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Ala A. Alhusban Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan

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Alaa M. Hammad Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan

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Lujain F. Alzaghari Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan

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Abstract

Purpose

Development and validation of a selective analytical method to accurately and precisely quantify nicotine and cotinine levels in rat's plasma after exposure to tobacco cigarettes and tobacco water-pipe.

Methods

An easy HPLC-Photodiode-Array Detection (PDA) method was developed and validated for simultaneous determination of nicotine and cotinine levels in plasma of 15 rats (10 rats after tobacco products exposure and 5 control rats). Nicotine and cotinine were extracted in one step from plasma using acetonitrile and concentrated to lowest volume using nitrogen stream.

Results

The developed method offered a rapid analysis time of 14 min with single step of analytes extraction from rat's plasma with recovery percentage range between 93 and 95% and excellent linearity with correlation factor more than 0.994 with analytical range between 50 and 1000 ng mL−1 and LOD of 25 ng mL−1 and 23 ng mL−1 for nicotine and cotinine, respectively. The analysis of rat's plasma after 28 days of exposure to tobacco cigarettes and tobacco water-pipe revealed that the average concentrations of 376 ng mL−1 for cotinine and 223 ng mL−1 for nicotine were obtained after tobacco cigarettes exposure, and 220 ng mL−1 for cotinine and 192 ng mL−1 for nicotine after tobacco water-pipe exposure.

Conclusion

Higher nicotine and cotinine levels were found in plasma after tobacco cigarettes exposure than water-pipe exposure which may have potential undesirable effects on passive smokers in both cases.

Abstract

Purpose

Development and validation of a selective analytical method to accurately and precisely quantify nicotine and cotinine levels in rat's plasma after exposure to tobacco cigarettes and tobacco water-pipe.

Methods

An easy HPLC-Photodiode-Array Detection (PDA) method was developed and validated for simultaneous determination of nicotine and cotinine levels in plasma of 15 rats (10 rats after tobacco products exposure and 5 control rats). Nicotine and cotinine were extracted in one step from plasma using acetonitrile and concentrated to lowest volume using nitrogen stream.

Results

The developed method offered a rapid analysis time of 14 min with single step of analytes extraction from rat's plasma with recovery percentage range between 93 and 95% and excellent linearity with correlation factor more than 0.994 with analytical range between 50 and 1000 ng mL−1 and LOD of 25 ng mL−1 and 23 ng mL−1 for nicotine and cotinine, respectively. The analysis of rat's plasma after 28 days of exposure to tobacco cigarettes and tobacco water-pipe revealed that the average concentrations of 376 ng mL−1 for cotinine and 223 ng mL−1 for nicotine were obtained after tobacco cigarettes exposure, and 220 ng mL−1 for cotinine and 192 ng mL−1 for nicotine after tobacco water-pipe exposure.

Conclusion

Higher nicotine and cotinine levels were found in plasma after tobacco cigarettes exposure than water-pipe exposure which may have potential undesirable effects on passive smokers in both cases.

1 Introduction

Nicotine, a pyridine alkaloid most abundant in tobacco leaves, is known as a highly addictive neurotoxin [1, 2]. The main source of nicotine is still tobacco smoking, which is listed as the main cause of cancer in many organs, especially in the respiratory system [3]. Tobacco smoking is associated with other chronic diseases including heart diseases, and hypertension [4, 5], as well as linked with high severity of COVID-19 infection [6]. In 2019, the WHO has reported that nearly third of the adults globally are habitually exposed to tobacco smoke [7]. In the same year, Jordan has been ranked among the world highest rate of smokers with 66% of males over 18 years were smoking cigarettes and/or shisha [8, 9]. Shisha, known locally as Argile or Nargile, is a water-pipe tobacco mixture mixed with fruit flavors [10]. Argile has recently grown in popularity among women and teenagers and led to a huge expansion in the number of waterpipe cafes [11]. Since argile supports nicotine dependence [12], it is necessary to determine the levels of nicotine and cotinine in plasma after argile exposure and compare it to tobacco cigarettes levels to evaluate which is more addictive and also influencer to both direct and passive smokers.

Cotinine is the major metabolite of nicotine [13, 14]. Almost 80% of inhaled nicotine, resulting from tobacco smoke exposure, is transformed into cotinine by CYP2A6 enzyme [15]. Due to its long half-life, cotinine is regularly determined in biological fluids including plasma as a biomarker of tobacco smoke exposure [16, 17].

Several methods, including immunoassays [18, 19] and spectroscopic techniques [20] have been used for the determination of nicotine and cotinine levels in physiological fluids. However, separation techniques have provided more selective approaches especially in complex matrices like plasma. Capillary electrophoresis is a powerful technique with high resolution power and selectivity particularly for metabolites determination in complex samples [21–23], and has been employed successfully for nicotine and cotinine quantification [24–26]. However, higher sensitivity has been provided by chromatographic techniques which are the most frequent methods used for quantification of both nicotine and cotinine in biological fluids. Gas chromatography has been employed widely for simultaneous determination of nicotine and cotinine in plasma [27–33]. Nevertheless, lengthy derivatization steps are usually required. Liquid chromatography (LC) is a preferable technique, as derivatization is now superfluous [34]. LC-MS [35, 36], and LC-MS/MS [37–40] have combined high sensitivity, simple extraction and rapid analysis. Yet, higher operational cost is still one of the main limitations of their use. HPLC-PDA can provide good sensitivity, rapid analysis and low running costs [41, 42], and has been employed efficiently for simultaneous determination of nicotine and cotinine in plasma [43–52].

The aim of this study was to develop and validate an easy, reliable and straightforward HPLC-PDA method for simultaneous determination of nicotine and cotinine content in rat plasma after tobacco cigarettes and water-pipe exposure.

2 Materials and methods

2.1 Chemicals

All reagents were analytical grade reagents obtained from Sigma–Aldrich (St. Louis, MO, USA) unless otherwise stated. All standard solutions were prepared exploiting Milli-Q water (Millipore, Bedford, MA, USA) and filtered using 0.22 μm syringe filter.

2.2 Instrumentation and HPLC–PDA analytical conditions

Waters 2690 Alliance HPLC system equipped with a Waters 996 photodiode array detector (Milford, MA, USA) was used for method development, validation and samples analysis. The analytical column used was C8- Widepore Aeris (4.6 × 250 mm, 3.6 µm) (Phenomenex, Torrance, CA, USA). The mobile phase consisted of potassium dihydrogen orthophosphate 0.272 gm and hexane sulphonic acid 0.182 gm in 1000 mL water and pH value was 3.2 adjusted with orthophosphoric acid: methanol (95%: 5%) in isocratic conditions and ambient temperature and was delivered at a flow rate of 1 mL min−1. Nicotine, cotinine and the IS (gallic acid) were identified at UV wavelengths between 210 and 400 nm and quantifications was carried out at 254 nm.

2.3 Calibration standards, quality control (QC) and samples preparations

Calibration curves (n = 3) were constructed for nicotine and cotinine measurement from seven standard solutions specifically: 50, 100, 200, 400, 600, 800, and 1000 ng mL−1. The standard solutions were prepared by serial dilution of proper amount from stock standard solutions (5 μg mL−1) with methanol (99.8%) and then were evaporated under nitrogen stream then reconstituted in 120 μl mobile phase, filtered using 0.22 μm syringe filter, and then 100 μl were injected into the HPLC column. Gallic acid was added as internal standard (IS) with conc. of 5 μg mL−1.

Following the aforementioned procedure, using concentrations of 50, 100, 200, 400, 600, 800, and 1000 ng mL−1 for both nicotine and cotinine, another calibration curves (n = 3) were constructed from 50, 100, 200, 400, 600, 800, and 1000 ng mL−1 for both nicotine and cotinine in rat plasma. Gallic acid was added as IS with conc. of 5 μg mL−1. The prepared standards were centrifuged at 15,000 rpm at 4°C, then the supernatants were taken and evaporated under nitrogen stream then reconstituted in 120 μl mobile phase, filtered using 0.22 μm syringe filter, and then 100 μl were injected. Moreover, QC's samples of nicotine and cotinine were prepared at 3 levels as QCL low (300 ng mL−1), QCM medium (700 ng mL−1), and QCH high (900 ng mL−1) in methanol and plasma.

For real sample preparations (control rats and rats exposed to tobacco cigarettes and water-pipe smokes), 100 μl of each sample was added to 500 μl acetonitrile (99.9%) and 5 μg mL−1 gallic acid, vortexed for 2 min. Then centrifuged at 15,000 rpm at 4°C then the supernatant were taken and evaporated under nitrogen stream then reconstituted in 120 μl mobile phase and then 100 μl was injected into the separation column.

2.4 Method validation

The developed analytical method was validated as follow:

2.4.1 Selectivity

Method selectivity is essential to discriminate nicotine, cotinine and gallic acid from endogenous substances and other compounds in rat plasma. The selectivity of the method was evaluated using a prepared rat plasma with no previous exposure to tobacco smoke, to ensure zero content of nicotine and cotinine, by comparing the peak signals at the target analyte retention times in blank samples with the peak signals at the target analyte retention time at limit of quantification (LOQ) samples.

2.4.2 Precision and accuracy

Inter-day and intra-day accuracy and precision were evaluated at 3 replicates of 3 QCs levels in one analytical run and three consecutive days respectively.

2.4.3 Limit of detection (LOD) and limit of quantification (LOQ)

The calculation of both LOD and LOQ were based on the Standard Deviation (SD) of intercepts of the calibration curves (σ) and the slope of the calibration curves (S) for both nicotine and cotinine standards (n = 3). The LOD and LOQ were expressed according to the following equations (standards and blanks injected 3 times consecutively):
LOD = ( 3.3 σ ) / S ⁡⁡⁡⁡⁡⁡⁡⁡⁡⁡⁡⁡ LOQ = ( 10 σ ) / S

The LOQ is the lowest reliable concentration in the calibration curve that could be quantified by the analytical method. In order to further validate the LOQ of the method experimentally, the analyte signal at the analyte retention time of a blank matrix was compared to the analyte signal at the same retention time of an LOQ sample prepared from the same matrix.

2.5 Tobacco cigarettes and water-pipe exposure to rats

2.5.1 Animals

Fifteen male Sprague-Dawley rats at the age of 10–12 weeks and weighing 180–250 g were inbred in Al-Zaytoonah University of Jordan (ZUJ). The room temperature was kept at 21°C ± 2°C and 50% ± 2% humidity with a 12-h light-dark cycle. All experiments were carried out during the light cycle. Sawdust was used as bedding and replaced regularly for hygienic purposes. The experimental and housing procedures were approved by the Institutional Animal Care and Use Committee at ZUJ, and conducted in accordance with the Helsinki guidelines for animal research [53]. Animals were randomly assigned into three groups. Fresh air or control group (n = 5), whole body cigarette exposed group (n = 5), and whole body waterpipe exposed group (n = 5). All groups had free access to water and food throughout the experiment. Control group was exposed to exposed to room air throughout the experiment. Tobacco cigarette and waterpipe groups were exposed to cigarette and waterpipe smoke, respectively for 2-h session/day for five days week−1, using whole body exposure apparatus.

2.5.2 Tobacco products used for exposure

LD blue cigarettes cruise (Liggett Ducat, 0.6 mg of nicotine, 0.8 mg of tar, and 0.01 mg of carbon monoxide), and Two-Apples flavor tobacco (Mazaya brand, Bahrain), which was purchased from local marketplace in Amman city, Jordan.

2.5.3 Cigarettes whole-body exposure (CE)

The timeline for control, cigarettes whole-body exposure, and waterpipe whole-body exposure, is illustrated in Fig. 1.

Fig. 1.
Fig. 1.

The timeline for control, cigarettes whole-body exposure, and waterpipe whole-body exposure groups used for rat exposure experiments

Citation: Acta Chromatographica 2022; 10.1556/1326.2022.01054

Cigarette whole-body exposure was achieved by placing the rats within an exposure chamber. The exposure chamber is made of acrylic and has dimensions of (40 × 40 × 40 cm), as shown in Fig. 2A. It includes a door in the upper part that allows the rats to be placed inside. For air circulation, the door contains three slots. Furthermore, the exposure chamber contains a cigarette inlet. The exposure chamber is connected to one pump, which has been modified and set to allow smoke from the cigarettes to enter the chamber via smoke tubes. A timer is linked to the exposure chamber to control the time for puffs (when the pump pulls cigarette smoke into the exposure chamber) and inter-puffs (during which the pump stop pulling the cigarette smoke into the exposure chamber). In this experiment, we defined a 3-s puff with a 30-s inter-puff, with a cycle that would be repeated throughout the duration of the exposure. Two cigarettes were used to saturate the exposure chamber after the rats were placed inside, and then the cigarettes were used in an orderly manner.

Fig. 2.
Fig. 2.

Scheme of chambers utilized for rat exposure to tobacco products showing the smoke inlets, pumps, and air inlets at the top. A: chamber used for rat exposure to tobacco cigarettes, B: chamber used for rat exposure to water-pipe

Citation: Acta Chromatographica 2022; 10.1556/1326.2022.01054

During the 2-h exposure period, twelve cigarettes were consumed. An electrochemical sensor (Monoxor II, Bacharach Inc. New Kensington, USA) was used to detect carbon monoxide (CO) levels in the exposure chamber. To manage the exposure process, the CO level was kept around 700 ppm. As a result, if the CO meter falls below 500 ppm, additional cigarettes were consumed, and if the CO meter rises beyond 899 ppm, the pump was turned off for 1–2 min to return the CO meter to the required range. In this experiment, the CO meter values varied from 500 to 800 ppm to ensure that the rats received an adequate dose of nicotine without suffocating, the average for each hour is presented in Table 1.

Table 1.

Carbon monoxide (CO) monitoring throughout the experiments days of exposures to tobacco cigarettes and water-pipe using

CO level (ppm) during the tobacco cigarettes exposure days (excluding days without exposure) CO level (ppm) during the water-pipe exposure days (excluding days without exposure)
Day no. 1st hour 2nd hour 1st hour 2nd hour
Day 1 510 509 567 939
Day 2 710 799 727 855
Day 3 667 663 744 877
Day 4 656 648 483 844
Day 5 616 620 755 857
Day 6 790 733 637 817
Day 7 806 742 731 836
Day 8 560 600 671 863
Day 9 557 610 835 895
Day 10 630 579 759 840
Day 11 613 610 867 921
Day 12 606 632 773 938
Day 13 637 646 830 919
Day 14 660 662 903 905
Day 15 669 700 755 862
Day 16 602 620 654 954
Day 17 614 790 74 859
Day 18 637 740 769 867
Day 19 639 700 808 937
Day 20 555 612 875 848
Average 636.7 660.8 744.2 881.6

2.5.4 Water-pipe whole-body exposure (WPE)

Whole-body exposure to waterpipe was accomplished in special box designed in our lab, which were linked to pre-programmed pumps. In this experiment, we defined a 3-s puff with a 17-s inter-puff, with a cycle that would be repeated throughout the duration of the exposure in the exposure chamber, as shown in Fig. 2B. During smoke exposure, ten grams of “Two Apples” flavor Bahraini maassel tobacco with 0.05% nicotine content and charcoal briquettes were put on the aluminum wrapped ceramic head, also 900 mL tap water was used in the waterpipe's water jar. Carbon monoxide (CO) levels in the exposure chamber were monitored using the Monoxor II electrochemical sensor, and the level of CO was maintained at 816.28 ± 91.73 ppm by either opening the box to fresh air and shutting down the exposure for 3–4 min when the levels reached about 999 ppm, or increasing the number of charcoal pieces or adding a new one if the CO levels were low about 600 ppm, the average for each hour is presented in Table 1. Refreshing charcoal was changed after an hour of exposure.

2.5.5 Blood sampling

Retro-orbital bleeding (ROB) tube was used to obtain three milliliters of blood which were collected in a heparinized tube, as previously mentioned [54]. After blood collection, the blood was kept at room temperature for 45 min before being centrifuged to extract plasma. The HERMIL, Z 230 A centrifuge (Hermil Labor Technik, Wehingen, Germany) was used for the centrifugation. The centrifuge method was carried for 35 min at 5500 rpm to separate the plasma, which was subsequently utilized for nicotine-cotinine concentration measurements using HPLC.

2.5.6 Statistical analysis

Data were compiled as means and standard errors of the means (SEM). One-way ANOVA followed by Tukey's multiple comparisons was used to investigate nicotine-cotinine plasma levels. All statistical analyses were done using Prism-GraphPad 9.0 and were based on a P < 0.05 level of significance.

3 Results and discussion

3.1 HPLC method development and validation

The development and validation of an analytical method for quantification of nicotine and cotinine in rat plasma samples has met the acceptance criteria of FDA guidelines [55]. In which the sample processing and preparation involved only a simple and effective one extraction step and dilution procedure where no carry over was reported of analytes. Moreover, the method was selective with no interfering peaks at the retention time of nicotine, cotinine and gallic acid were observed. Figure 3A demonstrates the chromatogram of analyzed rat plasma spiked with target analytes showing gallic acid, cotinine and nicotine peaks at 5.820, 9.583 and 11.713 min, respectively. Whereas, Fig. 3B presents the chromatogram of control rat plasma without spiking with any of target analytes. Likewise, the method showed excellent linearity with correlation factor equal to 0.9947 and 0.9951 over the analytical range of 100–1000 ng mL−1 with LOD of 25 ng mL−1 and 23 ng mL−1, and LOQ of 76 ng mL−1 and 71 ng mL−1 for nicotine and cotinine, respectively.

Fig. 3.
Fig. 3.

A: Chromatogram of rat plasma spiked with the target analytes (5000 ng mL−1 Gallic acid IS t R = 5.820 min, 400 ng mL−1 Cotinine t R = 9.583 min, and 400 ng mL−1 Nicotine t R = 11.713 min). B: chromatogram of control not-spiked rat plasma. The following chromatographic condition were applied: injection volume: 100 μL; column: C8- Widepore Aeris (4.6 X 250 mm, 3.6 µm); detector: UV wavelengths between 210 and 400 nm; and quantifications carried out at 254 nm

Citation: Acta Chromatographica 2022; 10.1556/1326.2022.01054

The accuracy of the method was performed by comparing the calibration curves in methanol to the calibration curves spiked in the rat plasma to calculate recovery % and study the matrix effect. The mean % recovery for spiked samples for nicotine was 94.83% and for cotinine was 93.34%. Moreover, intra-day and inter-day precisions were 3.324%, 4.005% and 2.006%, 2.322% for both nicotine and cotinine, respectively. Validation parameters were calculated and summarized in Table 2. This indicates that the developed method is reliable, accurate and reproducible.

Table 2.

Summarized results of chromatographic method validation parameters including, retention times (t R ), Calibration curve equations, limit of detection (LOD), limit of quantification (LOQ), linearity (R 2), analytes concentration within specific linearity range (ng mL−1), inter-day and intra-day accuracy and precision (RSD %) for multi number of injections (n) and percent recovery for nicotine and cotinine for HPLC with PDA detector

Parameter Nicotine value Cotinine value
Standards t R average (min) ± SD 11.713 ± 0.21 9.583 ± 0.15
Calibration curve equation y = 82.82× − 2578.10 y = 100.58× − 6551.80
Determination coefficient (R 2) 0.9947 0.9951
LOD 25 ng mL−1 23 ng mL−1
LOQ 76 ng mL−1 71 ng mL−1
Recovery 94.83% 93.34%
Intra-day accuracy 98.61% 98.34%
Intra-day precision 3.324% 2.006%
Inter-day accuracy 97.07% 97.38%
Inter-day precision 4.005% 2.322%

3.2 Nicotine and cotinine concentrations in rat's plasma

This study focuses on development and validation of a simple and straightforward HPLC method for selective determination of nicotine and cotinine content in plasma of experimental rats. Table 3 presents the description and labeling of rats, exposure type, duration and date of exposure, and cotinine and nicotine plasma levels after exposure to tobacco cigarettes and water-pipe. Several studies have been conducted for simultaneous determination and quantification of nicotine and cotinine using HPLC-PDA. The developed methods validation findings are summarized in Table 4. The general protocol for previous methods included several steps for extraction of nicotine and cotinine from plasma samples. For example, Shaik et al. [44] and Massadeh et al. [47] followed the following the protocol by which an aliquot of plasma was firstly alkalinized with NaOH, and then vortexed and centrifuged before extraction with dichloromethane-diethyl ether and then followed by vortex and centrifuging. After that, the organic layer was mixed with HCl and then evaporated under a stream of nitrogen until dryness and later reconstituted in mobile phase before injection into HPLC for analysis [44, 47]. Moreover, Nakajima et al. used the same protocol steps with deferent solvents [50]. Other methods proposed additional solid-phase extraction steps which increased the costs as well as time of analysis [45, 46]. In this study, the developed involved minimal extraction steps, only vortexing and centrifuging of plasma samples followed by evaporating and reconstituting of the supernatant with mobile phase before injection into C8 column in the HPLC system are required to obtain accurate and selective quantification, which provide a cost-effective and straightforward way. Moreover, the cost of all solvents and chemicals were selected to cut the cost of the method to obtain highly selective simultaneous analysis of nicotine and cotinine in plasma samples. The developed method have shown comparable validation results in terms of LODs, analysis time, recovery, and column type with other methods. The simplicity and speed of the developed method can be considered as advantages for its use for routine analysis of nicotine and cotinine in plasma samples.

Table 3.

The description of rats, exposure type, duration and date, and cotinine and nicotine plasma levels (all rats were obtained from ZUJ)

Rat label Starting date of exposure Duration of exposure Type of exposure Cotinine (ng mL−1) ± SD Nicotine (ng mL−1) ± SD
Rat 1T 10 Sept, 2021 28 Days Tobacco Cigarettes 363.87 ± 3.17 224.31 ± 14.23
Rat 2T 10 Sept, 2021 28 Days Tobacco Cigarettes 267.34 ± 1.27 222.19 ± 12.81
Rat 3T 10 Sept, 2021 28 Days Tobacco Cigarettes 409.04 ± 27.72 219.15 ± 8.94
Rat 4T 10 Sept, 2021 28 Days Tobacco Cigarettes 460.61 ± 35.58 227.42 ± 8.33
Rat 5T 10 Sept, 2021 28 Days Tobacco Cigarettes 379.72 ± 7.41 221.84 ± 13.23
Rat 1W 10 Sept, 2021 28 Days Water pipe 217.72 ± 6.40 189.29 ± 22.28
Rat 2W 10 Sept, 2021 28 Days Water pipe 248.28 ± 9.33 202.03 ± 10.61
Rat 3W 10 Sept, 2021 28 Days Water pipe 203.23 ± 13.19 193.21 ± 9.02
Rat 4W 10 Sept, 2021 28 Days Water pipe 221.69 ± 20.05 178.39 ± 17.11
Rat 5W 10 Sept, 2021 28 Days Water pipe 209.97 ± 16.10 199.02 ± 11.74
Rat 1C 10 Sept, 2021 28 Days Control (no exposure) Below LOQ Below LOQ
Rat 2C 10 Sept, 2021 28 Days Control (no exposure) Below LOQ Below LOQ
Rat 3C 10 Sept, 2021 28 Days Control (no exposure) Below LOQ Below LOQ
Rat 4C 10 Sept, 2021 28 Days Control (no exposure) Below LOQ Below LOQ
Rat 5C 10 Sept, 2021 28 Days Control (no exposure) Below LOQ Below LOQ
Table 4.

Summary of methods validation findings in the literature for nicotine and cotinine quantification in plasma after exposure to tobacco products using HPLC-PDA

Literature Column type Matrix LOD of nicotine and cotinine (ng mL−1) Analysis time (min) % Recovery nicotine and cotinine Country
Baj et al. [43] C18 Plasma 1.5 and 1.59 12 102.5 and 100.2 Poland
Shaik et al. [44] C18 Plasma NA 10 NA India
Papadoyannis et al. [45] C8 Plasma 10 and 10 15 94.2 and 93.3 Greece
Dawson et al. [46] C18 Plasma 8 and 13.6 20 51 and 64 USA
Massadeh et al. [47] C18 Plasma 0.32 and 0.26 16 96 and 95.8 Jordan
Abu-Qare et al. [48] C18 Plasma 20 and 150 17 84.7 and 80.1 USA
Abu-Qare et al. [49] C18 Plasma 20 and 30 11 85.8 and 81 USA
Nakajima et al. [50] C18 Plasma 0.2 and 1 20 103.3 and 82.1 Japan
Sioufi et al. [51] C18 Plasma 1 and 20 18 90 and 92 France
Hariharan et al. [52] C18 Plasma 1 and 3 10 94 and 96 USA
This study C8 Plasma 25 and 23 12 94.8 and 93.3 Jordan

3.3 Effect of whole-body cigarettes exposure and whole-body waterpipe exposure on cotinine and nicotine plasma concentration

Whole-body cigarettes exposure and whole-body waterpipe exposure for 4 weeks have a great effect on cotinine and nicotine plasma concentration compared to control group, as shown in Fig. 4A and 4B, respectively. High cotinine and nicotine plasma concentration was observed in the CE and the WPE groups but not Control group, which were exposed to fresh air room only. Furthermore, cotinine and nicotine plasma concentration in CE group was higher than cotinine and nicotine concentration in WPE group. This pattern of effect was confirmed by One-way ANOVA revealing a significant main effect of Treatment in cotinine plasma concentration [F (2, 12) =100.1, P < 0.0001; Fig. 4A] and a significant main effect of Treatment in nicotine plasma concentration [F (2, 12) = 2299, P < 0.0001; Fig. 4B]. Turkey's multiple comparison showed that there were significant increase in cotinine and nicotine plasma concentration in the CE and WPE groups compared to Control group, also there were a significant increase in cotinine and nicotine plasma concentration in CE group compared to WPE group (***P < 0.001, ****P < 0.0001).

Fig. 4.
Fig. 4.

Cotinine and nicotine plasma concentration in male rats (mean ± SEM) after exposure for 4 weeks. A: One-Way ANOVA showed an increase in cotinine plasma concentration in CE, and WPE groups compared to Control group, also there was an increase in cotinine plasma concentration in CE group compared to WPE group (***P < 0.001, ****P < 0.0001), (n = 5 for each group). B: Nicotine plasma concentration in male rats (mean ± SEM) after exposure for 4 weeks. One-Way ANOVA showed an increase in nicotine plasma concentration in CE, and WPE groups compared to Control group, also there was an increase in nicotine plasma concentration in CE group compared to WPE group (***P < 0.001, ****P < 0.0001), (n = 5 for each group)

Citation: Acta Chromatographica 2022; 10.1556/1326.2022.01054

Conclusion

The developed HPLC-PDA method was successfully applied accurately and precisely for ridable simultaneous determination of nicotine and cotinine content in plasma samples after exposure to different tobacco products. The validated method was simple, cost effective, and straightforward for determination of nicotine and cotinine in less than 12 min lower nicotine and cotinine concentrations in rat's plasma exist after exposure to water-pipe and tobacco cigarettes. However, the data obtained shows that exposure to both tobacco products is harmful to both direct and passive smokers.

Competing interests

The authors declare no competing interests.

Acknowledgments

This work was supported by the Deanship of Scientific Research at Al-Zaytoonah University of Jordan (2019–2020/23/6).

References

  • 1.

    Mazumder, S. ; Shia, W. ; Bendik, P.B. ; Achilihu, H. ; Sosnoff, C.S. ; Alexander, J.R. ; Luo, Z. ; Zhu, W. ; Pine, B.N. ; Feng, J. Nicotine exposure in the US population: total urinary nicotine biomarkers in NHANES 2015–2016. Int. J. Environ. Res. Public Health 2022, 19, 3660.

    • Search Google Scholar
    • Export Citation
  • 2.

    Taujenis, L. ; Olšauskaitė, V. ; Padarauskas, A. Determination of nicotine and three minor alkaloids in tobacco by hydrophilic interaction chromatography-tandem mass spectrometry. Acta Chromatographica 2015, 27, 373385.

    • Search Google Scholar
    • Export Citation
  • 3.

    Lu, F. ; Yu, M. ; Chen, C. ; Liu, L. ; Zhao, P. ; Shen, B. ; Sun, R. The emission of VOCs and CO from heated tobacco products, electronic cigarettes, and conventional cigarettes, and their health risk. Toxics 2021, 10, 8.

    • Search Google Scholar
    • Export Citation
  • 4.

    Dimitriadis, K. ; Narkiewicz, K. ; Leontsinis, I. ; Konstantinidis, D. ; Mihas, C. ; Andrikou, I. ; Thomopoulos, C. ; Tousoulis, D. ; Tsioufis, K. Acute effects of electronic and tobacco cigarette smoking on sympathetic nerve activity and blood pressure in humans. Int. J. Environ. Res. Public Health 2022, 19, 3237.

    • Search Google Scholar
    • Export Citation
  • 5.

    Hemmo, S.I. ; Naser, A.Y. ; Alwafi, H. ; Mansour, M.M. ; Alanazi, A.F. ; Jalal, Z. ; Alsairafi, Z.K. ; Paudyal, V. ; Alomari, E. ; Al-Momani, H. ; Al Bawab, A.Q. Hospital admissions due to ischemic heart diseases and prescriptions of cardiovascular diseases medications in England and Wales in the past two decades. Int. J. Environ. Res. Public Health 2021, 18, 7041.

    • Search Google Scholar
    • Export Citation
  • 6.

    Citu, I.M. ; Citu, C. ; Gorun, F. ; Neamtu, R. ; Motoc, A. ; Burlea, B. ; Rosca, O. ; Bratosin, F. ; Hosin, S. ; Manolescu, D. Using the NYHA classification as forecasting tool for hospital readmission and mortality in heart failure patients with COVID-19. J. Clin. Med. 2022, 11, 1382.

    • Search Google Scholar
    • Export Citation
  • 7.

    W.H. Organization . WHO Global Report on Trends in Prevalence of Tobacco Smoking 2000-2025; World Health Organization, 2018.

  • 8.

    W.H. Organisation . Empowering the Government of Jordan to Strengthen Tobacco Control, 2020.

  • 9.

    Nakkash, R. ; Khader, Y. ; Chalak, A. ; Abla, R. ; Abu-Rmeileh, N.M. ; Mostafa, A. ; Jawad, M. ; Lee, J.-H. ; Salloum, R.G. Prevalence of cigarette and waterpipe tobacco smoking among adults in three Eastern Mediterranean countries: a cross-sectional household survey. BMJ open 2022, 12, e055201.

    • Search Google Scholar
    • Export Citation
  • 10.

    Shihadeh, A. Investigation of mainstream smoke aerosol of the argileh water pipe. Food Chem. Toxicol. 2003, 41, 143152.

  • 11.

    Burki, T.K. Tobacco control in Jordan. Lancet Respir. Med. 2019, 7, 386.

  • 12.

    Aboaziza, E. ; Eissenberg, T. Waterpipe tobacco smoking: what is the evidence that it supports nicotine/tobacco dependence? Tob. Control 2015, 24, i44i53.

    • Search Google Scholar
    • Export Citation
  • 13.

    Mohd Radzi, N.A. ; Saub, R. ; Mohd Yusof, Z.Y. ; Dahlui, M. ; Sujak, S.L. Nicotine dependence among adolescents single and dual cigarette users. Children 2021, 8, 144.

    • Search Google Scholar
    • Export Citation
  • 14.

    Lkhagvadorj, K. ; Zeng, Z. ; Meyer, K.F. ; Verweij, L.P. ; Kooistra, W. ; Reinders-Luinge, M. ; Dijkhuizen, H.W. ; de Graaf, I.A. ; Plösch, T. ; Hylkema, M.N. Postnatal smoke exposure further increases the hepatic nicotine metabolism in prenatally smoke exposed male offspring and is linked with aberrant Cyp2a5 methylation. Int. J. Mol. Sci. 2020, 22, 164.

    • Search Google Scholar
    • Export Citation
  • 15.

    Hukkanen, J. ; Jacob, P. ; Benowitz, N.L. Metabolism and disposition kinetics of nicotine. Pharmacol. Rev. 2005, 57, 79115.

  • 16.

    Squillacioti, G. ; Bellisario, V. ; Grignani, E. ; Mengozzi, G. ; Bardaglio, G. ; Dalmasso, P. ; Bono, R. The asti study: the induction of oxidative stress in a population of children according to their body composition and passive tobacco smoking exposure. Int. J. Environ. Res. Public Health 2019, 16, 490.

    • Search Google Scholar
    • Export Citation
  • 17.

    Benowitz, N.L. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol. Rev. 1996, 18, 188204.

  • 18.

    Park, S. ; Lee, D.-H. ; Park, J.-G. ; Lee, Y.T. ; Chung, J. A sensitive enzyme immunoassay for measuring cotinine in passive smokers. Clin. Chim. Acta 2010, 411, 12381242.

    • Search Google Scholar
    • Export Citation
  • 19.

    Dhar, P. Measuring tobacco smoke exposure: quantifying nicotine/cotinine concentration in biological samples by colorimetry, chromatography and immunoassay methods. J. Pharm. Biomed. Anal. 2004, 35, 155168.

    • Search Google Scholar
    • Export Citation
  • 20.

    Mamián-López, M.B. ; Poppi, R.J. Standard addition method applied to the urinary quantification of nicotine in the presence of cotinine and anabasine using surface enhanced Raman spectroscopy and multivariate curve resolution. Anal. Chim. Acta 2013, 760, 5359.

    • Search Google Scholar
    • Export Citation
  • 21.

    Alhusban, A.A. ; Breadmore, M.C. ; Gueven, N. ; Guijt, R.M. Time-resolved pharmacological studies using automated, on-line monitoring of five parallel suspension cultures. Sci. Rep. 2017, 7, 19.

    • Search Google Scholar
    • Export Citation
  • 22.

    Alhusban, A.A. ; Hamadneh, L.A. ; Albustanji, S. ; Shallan, A.I. Lactate and pyruvate levels correlation with lactate dehydrogenase gene expression and glucose consumption in Tamoxifen-resistant MCF-7 cells using capillary electrophoresis with contactless conductivity detection (CE-C4D). Electrophoresis 2021.

    • Search Google Scholar
    • Export Citation
  • 23.

    Hamadneh, L. ; Al-Lakkis, L. ; Alhusban, A.A. ; Tarawneh, S. ; Abu-Irmaileh, B. ; Albustanji, S. ; Al-Bawab, A.Q. Changes in lactate production, lactate dehydrogenase genes expression and DNA methylation in response to tamoxifen resistance development in MCF-7 cell line. Genes 2021, 12, 777.

    • Search Google Scholar
    • Export Citation
  • 24.

    Baidoo, E.E. ; Clench, M.R. ; Smith, R.F. ; Tetler, L.W. Determination of nicotine and its metabolites in urine by solid-phase extraction and sample stacking capillary electrophoresis-mass spectrometry. J. Chromatogr. B 2003, 796, 303313.

    • Search Google Scholar
    • Export Citation
  • 25.

    Sun, J. ; Du, H. ; You, T. Determination of nicotine and its metabolite cotinine in urine and cigarette samples by capillary electrophoresis coupled with electrochemiluminescence. Electrophoresis 2011, 32, 21482154.

    • Search Google Scholar
    • Export Citation
  • 26.

    Nuchtavorn, N. ; Ryvolova, M. ; Bek, F. ; Macka, M. ; Phechkrajang, C. ; Suntornsuk, L. Potential of capillary electrophoresis (CE) and chip-CE with dual detection (capacitively-coupled contactless conductivity detection (C4D) and fluorescence Detection) for monitoring of nicotine and cotinine derivatization. Anal. Sci. 2013, 29, 339344.

    • Search Google Scholar
    • Export Citation
  • 27.

    Shin, H.-S. ; Kim, J.-G. ; Shin, Y.-J. ; Jee, S.H. Sensitive and simple method for the determination of nicotine and cotinine in human urine, plasma and saliva by gas chromatography–mass spectrometry. J. Chromatogr. B 2002, 769, 177183.

    • Search Google Scholar
    • Export Citation
  • 28.

    Jacob, P., III ; Wu, S. ; Yu, L. ; Benowitz, N.L. Simultaneous determination of mecamylamine, nicotine, and cotinine in plasma by gas chromatography-mass spectrometry. J. Pharm. Biomed. Anal. 2000, 23, 653661.

    • Search Google Scholar
    • Export Citation
  • 29.

    Curvall, M. ; Kazemi-Vala, E. ; Enzell, C.R. Simultaneous determination of nicotine and cotinine in plasma using capillary column gas chromatography with nitrogen-sensitive detection. J. Chromatogr. B: Biomed. Sci. Appl. 1982, 232, 283293.

    • Search Google Scholar
    • Export Citation
  • 30.

    Deutsch, J. ; Hegedus, L. ; Greig, N.H. ; Rapoport, S.I. ; Soncrant, T.T. Electron-impact and chemical ionization detection of nicotine and cotinine by gas chromatography—mass spectrometry in rat plasma and brain. J. Chromatogr. B: Biomed. Sci. Appl. 1992, 579, 9398.

    • Search Google Scholar
    • Export Citation
  • 31.

    Cognard, E. ; Staub, C. Determination of Nicotine and its Major Metabolite Cotinine in Plasma or Serum by Gas Chromatography-Mass Spectrometry Using Ion-Trap Detection, 2003.

    • Search Google Scholar
    • Export Citation
  • 32.

    Kogan, M. ; Verebey, K. ; Jaffee, J. ; Mule, S. Simultaneous determination of nicotine and cotinine in human plasma by nitrogen detection gas-liquid chromatography. J. Forensic Sci. 1981, 26, 611.

    • Search Google Scholar
    • Export Citation
  • 33.

    Hammes, W. ; Bittner, J. ; Müller, R. Simultaneous determination of nicotine and cotinine in plasma by capillary gas liquid chromatography with nitrogen-sensitive detection. Fresenius' Z. für analytische Chem. 1989, 333, 745746.

    • Search Google Scholar
    • Export Citation
  • 34.

    Lee, S. ; Nath, C.E. ; Balzer, B.W. ; Lewis, C.R. ; Trahair, T.N. ; Anazodo, A.C. ; Shaw, P.J. An HPLC–PDA method for determination of alectinib concentrations in the plasma of an adolescent. Acta Chromatographica 2020, 32, 166169.

    • Search Google Scholar
    • Export Citation
  • 35.

    Kim, I. ; Huestis, M.A. A validated method for the determination of nicotine, cotinine, trans-3′-hydroxycotinine, and norcotinine in human plasma using solid-phase extraction and liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. J. Mass Spectrom. 2006, 41, 815821.

    • Search Google Scholar
    • Export Citation
  • 36.

    Jin, S. ; Pang, W. ; Zhao, L. ; Zhao, Z. ; Mei, S. Review of HPLC–MS methods for the analysis of nicotine and its active metabolite cotinine in various biological matrices. Biomed. Chromatogr. 2022, e5351.

    • Search Google Scholar
    • Export Citation
  • 37.

    Shakleya, D.M. ; Huestis, M.A. Simultaneous and sensitive measurement of nicotine, cotinine, trans-3′-hydroxycotinine and norcotinine in human plasma by liquid chromatography-tandem mass spectrometry. J. Chromatogr. B 2009, 877, 35373542.

    • Search Google Scholar
    • Export Citation
  • 38.

    Stolker, A.L.A. ; Niesing, W. ; Hogendoorn, E.A. ; Rambali, A.B. ; Vleeming, W. Determination of nicotine and cotinine in rat plasma by liquid chromatography–tandem mass spectrometry. J. Chromatogr. A. 2003, 1020, 3543.

    • Search Google Scholar
    • Export Citation
  • 39.

    Xu, A.S. ; Peng, L.L. ; Havel, J.A. ; Petersen, M.E. ; Fiene, J.A. ; Hulse, J.D. Determination of nicotine and cotinine in human plasma by liquid chromatography-tandem mass spectrometry with atmospheric-pressure chemical ionization interface. J. Chromatogr. B: Biomed. Sci. Appl. 1996, 682, 249257.

    • Search Google Scholar
    • Export Citation
  • 40.

    Alhusban, A.A. ; Albustanji, S. ; Hamadneh, L.A. ; Shallan, A.I. High performance liquid chromatography–tandem mass spectrometry method for correlating the metabolic changes of lactate, pyruvate and L-glutamine with induced tamoxifen resistant MCF-7 cell line potential molecular changes. Molecules 2021, 26, 4824.

    • Search Google Scholar
    • Export Citation
  • 41.

    Alhusban, A.A. ; Ata, S.A. Simple HPLC method for rapid quantification of nicotine content in e-cigarettes liquids. Acta Chromatographica 2021, 33, 302307.

    • Search Google Scholar
    • Export Citation
  • 42.

    Karvaly, G.B. ; Tekes, K. ; Szimrók, Z. ; FŰrÉsz, J. ; KuČa, K. ; Kalász, H. A fieldable, high-throughput, cost-efficient high performance liquid chromatography-ultraviolet absorption detection (HPLC-UV) method for the quantitation of bispyridinium quaternary aldoxime cholinesterase reactivators in blood. Acta Chromatographica 2021, 33, 134144.

    • Search Google Scholar
    • Export Citation
  • 43.

    Baj, J. ; Flieger, W. ; Przygodzka, D. ; Buszewicz, G. ; Teresiński, G. ; Pizoń, M. ; Maciejewski, R. ; Flieger, J. Application of HPLC-QQQ-MS/MS and new RP-HPLC-DAD system utilizing the chaotropic effect for determination of nicotine and its major metabolites cotinine, and trans-3′-hydroxycotinine in human plasma samples. Molecules 2022, 27, 682.

    • Search Google Scholar
    • Export Citation
  • 44.

    Shaik, F.B. ; Nagajothi, G. ; Swarnalatha, K. ; Kumar, C.S. ; Maddu, N. Quantification of nicotine and cotinine in plasma, saliva, and urine by HPLC method in chewing tobacco users. Asian Pac. J. Cancer Prev: APJCP 2019, 20, 3617.

    • Search Google Scholar
    • Export Citation
  • 45.

    Papadoyannis, I. ; Samanidou, V. ; Stefanidou, P. Clinical assay of nicotine and its metabolite, cotinine, in body fluids by HPLC following solid phase extraction. J. liquid Chromatogr. Relat. Tech. 2002, 25, 23152335.

    • Search Google Scholar
    • Export Citation
  • 46.

    Dawson, R. ; Messina, S. ; Stokes, C. ; Salyani, S. ; Alcalay, N. ; De Fiebre, N. ; De Fiebre, C. Solid-phase extraction and HPLC assay of nicotine and cotinine in plasma and brain. Toxicol. Mech. Methods 2002, 12, 4558.

    • Search Google Scholar
    • Export Citation
  • 47.

    Massadeh, A.M. ; Gharaibeh, A.A. ; Omari, K.W. A single-step extraction method for the determination of nicotine and cotinine in Jordanian smokers' blood and urine samples by RP-HPLC and GC-MS. J. Chromatogr. Sci. 2009, 47, 170177.

    • Search Google Scholar
    • Export Citation
  • 48.

    Abu-Qare, A.W. ; Abou-Donia, M.B. Quantification of nicotine, chlorpyrifos and their metabolites in rat plasma and urine using high-performance liquid chromatography. J. Chromatogr. B: Biomed. Sci. Appl. 2001, 757, 295300.

    • Search Google Scholar
    • Export Citation
  • 49.

    Abu-Qare, A.W. ; Abou-Donia, M.B. High-performance liquid chromatographic determination of pyridostigmine bromide, nicotine, and their metabolites in rat plasma and urine. J. Chromatogr. Sci. 2001, 39, 287292.

    • Search Google Scholar
    • Export Citation
  • 50.

    Nakajima, M. ; Yamamoto, T. ; Kuroiwa, Y. ; Yokoi, T. Improved highly sensitive method for determination of nicotine and cotinine in human plasma by high-performance liquid chromatography. J. Chromatogr. B: Biomed. Sci. Appl. 2000, 742, 211215.

    • Search Google Scholar
    • Export Citation
  • 51.

    Sioufi, A. ; Parisot, C. ; Sandrenan, N. ; Dubois, J. High performance liquid chromatographic determination of nicotine and cotinine in plasma and nicotine and cotinine, simultaneously, in urine. Methods Find. Exp. Clin. Pharmacol. 1989, 11, 179185.

    • Search Google Scholar
    • Export Citation
  • 52.

    Hariharan, M. ; VanNoord, T. ; Greden, J.F. A high-performance liquid-chromatographic method for routine simultaneous determination of nicotine and cotinine in plasma. Clin. Chem. 1988, 34, 724729.

    • Search Google Scholar
    • Export Citation
  • 53.

    Emanuel, E.J. ; Grady, C.C. ; Crouch, R.A. ; Lie, R.K. ; Miller, F.G. ; Wendler, D.D. The Oxford Textbook of Clinical Research Ethics; Oxford University Press, 2008.

    • Search Google Scholar
    • Export Citation
  • 54.

    Sharma, A. ; Fish, B.L. ; Moulder, J.E. ; Medhora, M. ; Baker, J.E. ; Mader, M. ; Cohen, E.P. Safety and blood sample volume and quality of a refined retro-orbital bleeding technique in rats using a lateral approach. Lab Animal 2014, 43, 6366.

    • Search Google Scholar
    • Export Citation
  • 55.

    FDA, Food and Drug Administration . Guidance for Industry: Bioanalytical Method Validation, 2001. https://www.fda.gov/downloads/drugs/guidances/ucm070107.Pdf (accessed Apr 12, 2020).

    • Search Google Scholar
    • Export Citation
  • 1.

    Mazumder, S. ; Shia, W. ; Bendik, P.B. ; Achilihu, H. ; Sosnoff, C.S. ; Alexander, J.R. ; Luo, Z. ; Zhu, W. ; Pine, B.N. ; Feng, J. Nicotine exposure in the US population: total urinary nicotine biomarkers in NHANES 2015–2016. Int. J. Environ. Res. Public Health 2022, 19, 3660.

    • Search Google Scholar
    • Export Citation
  • 2.

    Taujenis, L. ; Olšauskaitė, V. ; Padarauskas, A. Determination of nicotine and three minor alkaloids in tobacco by hydrophilic interaction chromatography-tandem mass spectrometry. Acta Chromatographica 2015, 27, 373385.

    • Search Google Scholar
    • Export Citation
  • 3.

    Lu, F. ; Yu, M. ; Chen, C. ; Liu, L. ; Zhao, P. ; Shen, B. ; Sun, R. The emission of VOCs and CO from heated tobacco products, electronic cigarettes, and conventional cigarettes, and their health risk. Toxics 2021, 10, 8.

    • Search Google Scholar
    • Export Citation
  • 4.

    Dimitriadis, K. ; Narkiewicz, K. ; Leontsinis, I. ; Konstantinidis, D. ; Mihas, C. ; Andrikou, I. ; Thomopoulos, C. ; Tousoulis, D. ; Tsioufis, K. Acute effects of electronic and tobacco cigarette smoking on sympathetic nerve activity and blood pressure in humans. Int. J. Environ. Res. Public Health 2022, 19, 3237.

    • Search Google Scholar
    • Export Citation
  • 5.

    Hemmo, S.I. ; Naser, A.Y. ; Alwafi, H. ; Mansour, M.M. ; Alanazi, A.F. ; Jalal, Z. ; Alsairafi, Z.K. ; Paudyal, V. ; Alomari, E. ; Al-Momani, H. ; Al Bawab, A.Q. Hospital admissions due to ischemic heart diseases and prescriptions of cardiovascular diseases medications in England and Wales in the past two decades. Int. J. Environ. Res. Public Health 2021, 18, 7041.

    • Search Google Scholar
    • Export Citation
  • 6.

    Citu, I.M. ; Citu, C. ; Gorun, F. ; Neamtu, R. ; Motoc, A. ; Burlea, B. ; Rosca, O. ; Bratosin, F. ; Hosin, S. ; Manolescu, D. Using the NYHA classification as forecasting tool for hospital readmission and mortality in heart failure patients with COVID-19. J. Clin. Med. 2022, 11, 1382.

    • Search Google Scholar
    • Export Citation
  • 7.

    W.H. Organization . WHO Global Report on Trends in Prevalence of Tobacco Smoking 2000-2025; World Health Organization, 2018.

  • 8.

    W.H. Organisation . Empowering the Government of Jordan to Strengthen Tobacco Control, 2020.

  • 9.

    Nakkash, R. ; Khader, Y. ; Chalak, A. ; Abla, R. ; Abu-Rmeileh, N.M. ; Mostafa, A. ; Jawad, M. ; Lee, J.-H. ; Salloum, R.G. Prevalence of cigarette and waterpipe tobacco smoking among adults in three Eastern Mediterranean countries: a cross-sectional household survey. BMJ open 2022, 12, e055201.

    • Search Google Scholar
    • Export Citation
  • 10.

    Shihadeh, A. Investigation of mainstream smoke aerosol of the argileh water pipe. Food Chem. Toxicol. 2003, 41, 143152.

  • 11.

    Burki, T.K. Tobacco control in Jordan. Lancet Respir. Med. 2019, 7, 386.

  • 12.

    Aboaziza, E. ; Eissenberg, T. Waterpipe tobacco smoking: what is the evidence that it supports nicotine/tobacco dependence? Tob. Control 2015, 24, i44i53.

    • Search Google Scholar
    • Export Citation
  • 13.

    Mohd Radzi, N.A. ; Saub, R. ; Mohd Yusof, Z.Y. ; Dahlui, M. ; Sujak, S.L. Nicotine dependence among adolescents single and dual cigarette users. Children 2021, 8, 144.

    • Search Google Scholar
    • Export Citation
  • 14.

    Lkhagvadorj, K. ; Zeng, Z. ; Meyer, K.F. ; Verweij, L.P. ; Kooistra, W. ; Reinders-Luinge, M. ; Dijkhuizen, H.W. ; de Graaf, I.A. ; Plösch, T. ; Hylkema, M.N. Postnatal smoke exposure further increases the hepatic nicotine metabolism in prenatally smoke exposed male offspring and is linked with aberrant Cyp2a5 methylation. Int. J. Mol. Sci. 2020, 22, 164.

    • Search Google Scholar
    • Export Citation
  • 15.

    Hukkanen, J. ; Jacob, P. ; Benowitz, N.L. Metabolism and disposition kinetics of nicotine. Pharmacol. Rev. 2005, 57, 79115.

  • 16.

    Squillacioti, G. ; Bellisario, V. ; Grignani, E. ; Mengozzi, G. ; Bardaglio, G. ; Dalmasso, P. ; Bono, R. The asti study: the induction of oxidative stress in a population of children according to their body composition and passive tobacco smoking exposure. Int. J. Environ. Res. Public Health 2019, 16, 490.

    • Search Google Scholar
    • Export Citation
  • 17.

    Benowitz, N.L. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol. Rev. 1996, 18, 188204.

  • 18.

    Park, S. ; Lee, D.-H. ; Park, J.-G. ; Lee, Y.T. ; Chung, J. A sensitive enzyme immunoassay for measuring cotinine in passive smokers. Clin. Chim. Acta 2010, 411, 12381242.

    • Search Google Scholar
    • Export Citation
  • 19.

    Dhar, P. Measuring tobacco smoke exposure: quantifying nicotine/cotinine concentration in biological samples by colorimetry, chromatography and immunoassay methods. J. Pharm. Biomed. Anal. 2004, 35, 155168.

    • Search Google Scholar
    • Export Citation
  • 20.

    Mamián-López, M.B. ; Poppi, R.J. Standard addition method applied to the urinary quantification of nicotine in the presence of cotinine and anabasine using surface enhanced Raman spectroscopy and multivariate curve resolution. Anal. Chim. Acta 2013, 760, 5359.

    • Search Google Scholar
    • Export Citation
  • 21.

    Alhusban, A.A. ; Breadmore, M.C. ; Gueven, N. ; Guijt, R.M. Time-resolved pharmacological studies using automated, on-line monitoring of five parallel suspension cultures. Sci. Rep. 2017, 7, 19.

    • Search Google Scholar
    • Export Citation
  • 22.

    Alhusban, A.A. ; Hamadneh, L.A. ; Albustanji, S. ; Shallan, A.I. Lactate and pyruvate levels correlation with lactate dehydrogenase gene expression and glucose consumption in Tamoxifen-resistant MCF-7 cells using capillary electrophoresis with contactless conductivity detection (CE-C4D). Electrophoresis 2021.

    • Search Google Scholar
    • Export Citation
  • 23.

    Hamadneh, L. ; Al-Lakkis, L. ; Alhusban, A.A. ; Tarawneh, S. ; Abu-Irmaileh, B. ; Albustanji, S. ; Al-Bawab, A.Q. Changes in lactate production, lactate dehydrogenase genes expression and DNA methylation in response to tamoxifen resistance development in MCF-7 cell line. Genes 2021, 12, 777.

    • Search Google Scholar
    • Export Citation
  • 24.

    Baidoo, E.E. ; Clench, M.R. ; Smith, R.F. ; Tetler, L.W. Determination of nicotine and its metabolites in urine by solid-phase extraction and sample stacking capillary electrophoresis-mass spectrometry. J. Chromatogr. B 2003, 796, 303313.

    • Search Google Scholar
    • Export Citation
  • 25.

    Sun, J. ; Du, H. ; You, T. Determination of nicotine and its metabolite cotinine in urine and cigarette samples by capillary electrophoresis coupled with electrochemiluminescence. Electrophoresis 2011, 32, 21482154.

    • Search Google Scholar
    • Export Citation
  • 26.

    Nuchtavorn, N. ; Ryvolova, M. ; Bek, F. ; Macka, M. ; Phechkrajang, C. ; Suntornsuk, L. Potential of capillary electrophoresis (CE) and chip-CE with dual detection (capacitively-coupled contactless conductivity detection (C4D) and fluorescence Detection) for monitoring of nicotine and cotinine derivatization. Anal. Sci. 2013, 29, 339344.

    • Search Google Scholar
    • Export Citation
  • 27.

    Shin, H.-S. ; Kim, J.-G. ; Shin, Y.-J. ; Jee, S.H. Sensitive and simple method for the determination of nicotine and cotinine in human urine, plasma and saliva by gas chromatography–mass spectrometry. J. Chromatogr. B 2002, 769, 177183.

    • Search Google Scholar
    • Export Citation
  • 28.

    Jacob, P., III ; Wu, S. ; Yu, L. ; Benowitz, N.L. Simultaneous determination of mecamylamine, nicotine, and cotinine in plasma by gas chromatography-mass spectrometry. J. Pharm. Biomed. Anal. 2000, 23, 653661.

    • Search Google Scholar
    • Export Citation
  • 29.

    Curvall, M. ; Kazemi-Vala, E. ; Enzell, C.R. Simultaneous determination of nicotine and cotinine in plasma using capillary column gas chromatography with nitrogen-sensitive detection. J. Chromatogr. B: Biomed. Sci. Appl. 1982, 232, 283293.

    • Search Google Scholar
    • Export Citation
  • 30.

    Deutsch, J. ; Hegedus, L. ; Greig, N.H. ; Rapoport, S.I. ; Soncrant, T.T. Electron-impact and chemical ionization detection of nicotine and cotinine by gas chromatography—mass spectrometry in rat plasma and brain. J. Chromatogr. B: Biomed. Sci. Appl. 1992, 579, 9398.

    • Search Google Scholar
    • Export Citation
  • 31.

    Cognard, E. ; Staub, C. Determination of Nicotine and its Major Metabolite Cotinine in Plasma or Serum by Gas Chromatography-Mass Spectrometry Using Ion-Trap Detection, 2003.

    • Search Google Scholar
    • Export Citation
  • 32.

    Kogan, M. ; Verebey, K. ; Jaffee, J. ; Mule, S. Simultaneous determination of nicotine and cotinine in human plasma by nitrogen detection gas-liquid chromatography. J. Forensic Sci. 1981, 26, 611.

    • Search Google Scholar
    • Export Citation
  • 33.

    Hammes, W. ; Bittner, J. ; Müller, R. Simultaneous determination of nicotine and cotinine in plasma by capillary gas liquid chromatography with nitrogen-sensitive detection. Fresenius' Z. für analytische Chem. 1989, 333, 745746.

    • Search Google Scholar
    • Export Citation
  • 34.

    Lee, S. ; Nath, C.E. ; Balzer, B.W. ; Lewis, C.R. ; Trahair, T.N. ; Anazodo, A.C. ; Shaw, P.J. An HPLC–PDA method for determination of alectinib concentrations in the plasma of an adolescent. Acta Chromatographica 2020, 32, 166169.

    • Search Google Scholar
    • Export Citation
  • 35.

    Kim, I. ; Huestis, M.A. A validated method for the determination of nicotine, cotinine, trans-3′-hydroxycotinine, and norcotinine in human plasma using solid-phase extraction and liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. J. Mass Spectrom. 2006, 41, 815821.

    • Search Google Scholar
    • Export Citation
  • 36.

    Jin, S. ; Pang, W. ; Zhao, L. ; Zhao, Z. ; Mei, S. Review of HPLC–MS methods for the analysis of nicotine and its active metabolite cotinine in various biological matrices. Biomed. Chromatogr. 2022, e5351.

    • Search Google Scholar
    • Export Citation
  • 37.

    Shakleya, D.M. ; Huestis, M.A. Simultaneous and sensitive measurement of nicotine, cotinine, trans-3′-hydroxycotinine and norcotinine in human plasma by liquid chromatography-tandem mass spectrometry. J. Chromatogr. B 2009, 877, 35373542.

    • Search Google Scholar
    • Export Citation
  • 38.

    Stolker, A.L.A. ; Niesing, W. ; Hogendoorn, E.A. ; Rambali, A.B. ; Vleeming, W. Determination of nicotine and cotinine in rat plasma by liquid chromatography–tandem mass spectrometry. J. Chromatogr. A. 2003, 1020, 3543.

    • Search Google Scholar
    • Export Citation
  • 39.

    Xu, A.S. ; Peng, L.L. ; Havel, J.A. ; Petersen, M.E. ; Fiene, J.A. ; Hulse, J.D. Determination of nicotine and cotinine in human plasma by liquid chromatography-tandem mass spectrometry with atmospheric-pressure chemical ionization interface. J. Chromatogr. B: Biomed. Sci. Appl. 1996, 682, 249257.

    • Search Google Scholar
    • Export Citation
  • 40.

    Alhusban, A.A. ; Albustanji, S. ; Hamadneh, L.A. ; Shallan, A.I. High performance liquid chromatography–tandem mass spectrometry method for correlating the metabolic changes of lactate, pyruvate and L-glutamine with induced tamoxifen resistant MCF-7 cell line potential molecular changes. Molecules 2021, 26, 4824.

    • Search Google Scholar
    • Export Citation
  • 41.

    Alhusban, A.A. ; Ata, S.A. Simple HPLC method for rapid quantification of nicotine content in e-cigarettes liquids. Acta Chromatographica 2021, 33, 302307.

    • Search Google Scholar
    • Export Citation
  • 42.

    Karvaly, G.B. ; Tekes, K. ; Szimrók, Z. ; FŰrÉsz, J. ; KuČa, K. ; Kalász, H. A fieldable, high-throughput, cost-efficient high performance liquid chromatography-ultraviolet absorption detection (HPLC-UV) method for the quantitation of bispyridinium quaternary aldoxime cholinesterase reactivators in blood. Acta Chromatographica 2021, 33, 134144.

    • Search Google Scholar
    • Export Citation
  • 43.

    Baj, J. ; Flieger, W. ; Przygodzka, D. ; Buszewicz, G. ; Teresiński, G. ; Pizoń, M. ; Maciejewski, R. ; Flieger, J. Application of HPLC-QQQ-MS/MS and new RP-HPLC-DAD system utilizing the chaotropic effect for determination of nicotine and its major metabolites cotinine, and trans-3′-hydroxycotinine in human plasma samples. Molecules 2022, 27, 682.

    • Search Google Scholar
    • Export Citation
  • 44.

    Shaik, F.B. ; Nagajothi, G. ; Swarnalatha, K. ; Kumar, C.S. ; Maddu, N. Quantification of nicotine and cotinine in plasma, saliva, and urine by HPLC method in chewing tobacco users. Asian Pac. J. Cancer Prev: APJCP 2019, 20, 3617.

    • Search Google Scholar
    • Export Citation
  • 45.

    Papadoyannis, I. ; Samanidou, V. ; Stefanidou, P. Clinical assay of nicotine and its metabolite, cotinine, in body fluids by HPLC following solid phase extraction. J. liquid Chromatogr. Relat. Tech. 2002, 25, 23152335.

    • Search Google Scholar
    • Export Citation
  • 46.

    Dawson, R. ; Messina, S. ; Stokes, C. ; Salyani, S. ; Alcalay, N. ; De Fiebre, N. ; De Fiebre, C. Solid-phase extraction and HPLC assay of nicotine and cotinine in plasma and brain. Toxicol. Mech. Methods 2002, 12, 4558.

    • Search Google Scholar
    • Export Citation
  • 47.

    Massadeh, A.M. ; Gharaibeh, A.A. ; Omari, K.W. A single-step extraction method for the determination of nicotine and cotinine in Jordanian smokers' blood and urine samples by RP-HPLC and GC-MS. J. Chromatogr. Sci. 2009, 47, 170177.

    • Search Google Scholar
    • Export Citation
  • 48.

    Abu-Qare, A.W. ; Abou-Donia, M.B. Quantification of nicotine, chlorpyrifos and their metabolites in rat plasma and urine using high-performance liquid chromatography. J. Chromatogr. B: Biomed. Sci. Appl. 2001, 757, 295300.

    • Search Google Scholar
    • Export Citation
  • 49.

    Abu-Qare, A.W. ; Abou-Donia, M.B. High-performance liquid chromatographic determination of pyridostigmine bromide, nicotine, and their metabolites in rat plasma and urine. J. Chromatogr. Sci. 2001, 39, 287292.

    • Search Google Scholar
    • Export Citation
  • 50.

    Nakajima, M. ; Yamamoto, T. ; Kuroiwa, Y. ; Yokoi, T. Improved highly sensitive method for determination of nicotine and cotinine in human plasma by high-performance liquid chromatography. J. Chromatogr. B: Biomed. Sci. Appl. 2000, 742, 211215.

    • Search Google Scholar
    • Export Citation
  • 51.

    Sioufi, A. ; Parisot, C. ; Sandrenan, N. ; Dubois, J. High performance liquid chromatographic determination of nicotine and cotinine in plasma and nicotine and cotinine, simultaneously, in urine. Methods Find. Exp. Clin. Pharmacol. 1989, 11, 179185.

    • Search Google Scholar
    • Export Citation
  • 52.

    Hariharan, M. ; VanNoord, T. ; Greden, J.F. A high-performance liquid-chromatographic method for routine simultaneous determination of nicotine and cotinine in plasma. Clin. Chem. 1988, 34, 724729.

    • Search Google Scholar
    • Export Citation
  • 53.

    Emanuel, E.J. ; Grady, C.C. ; Crouch, R.A. ; Lie, R.K. ; Miller, F.G. ; Wendler, D.D. The Oxford Textbook of Clinical Research Ethics; Oxford University Press, 2008.

    • Search Google Scholar
    • Export Citation
  • 54.

    Sharma, A. ; Fish, B.L. ; Moulder, J.E. ; Medhora, M. ; Baker, J.E. ; Mader, M. ; Cohen, E.P. Safety and blood sample volume and quality of a refined retro-orbital bleeding technique in rats using a lateral approach. Lab Animal 2014, 43, 6366.

    • Search Google Scholar
    • Export Citation
  • 55.

    FDA, Food and Drug Administration . Guidance for Industry: Bioanalytical Method Validation, 2001. https://www.fda.gov/downloads/drugs/guidances/ucm070107.Pdf (accessed Apr 12, 2020).

    • Search Google Scholar
    • Export Citation
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Senior editors

Editor(s)-in-Chief: Kowalska, Teresa

Editor(s)-in-Chief: Sajewicz, Mieczyslaw

Editors(s)

  • Danica Agbaba (University of Belgrade, Belgrade, Serbia)
  • Ivana Stanimirova-Daszykowska (University of Silesia, Katowice, Poland)
  • Monika Waksmundzka-Hajnos (Medical University of Lublin, Lublin, Poland)

Editorial Board

  • R. Bhushan (The Indian Institute of Technology, Roorkee, India)
  • J. Bojarski (Jagiellonian University, Kraków, Poland)
  • B. Chankvetadze (State University of Tbilisi, Tbilisi, Georgia)
  • M. Daszykowski (University of Silesia, Katowice, Poland)
  • T.H. Dzido (Medical University of Lublin, Lublin, Poland)
  • A. Felinger (University of Pécs, Pécs, Hungary)
  • K. Glowniak (Medical University of Lublin, Lublin, Poland)
  • B. Glód (Siedlce University of Natural Sciences and Humanities, Siedlce, Poland)
  • A. Gumieniczek (Medical University of Lublin, Lublin, Poland)
  • U. Hubicka (Jagiellonian University, Kraków, Poland)
  • K. Kaczmarski (Rzeszow University of Technology, Rzeszów, Poland)
  • H. Kalász (Semmelweis University, Budapest, Hungary)
  • K. Karljiković Rajić (University of Belgrade, Belgrade, Serbia)
  • I. Klebovich (Semmelweis University, Budapest, Hungary)
  • A. Koch (Private Pharmacy, Hamburg, Germany)
  • Ł. Komsta (Medical University of Lublin, Lublin, Poland)
  • P. Kus (Univerity of Silesia, Katowice, Poland)
  • D. Mangelings (Free University of Brussels, Brussels, Belgium)
  • E. Mincsovics (Corvinus University of Budapest, Budapest, Hungary)
  • G. Morlock (Giessen University, Giessen, Germany)
  • A. Petruczynik (Medical University of Lublin, Lublin, Poland)
  • R. Skibiński (Medical University of Lublin, Lublin, Poland)
  • B. Spangenberg (Offenburg University of Applied Sciences, Germany)
  • T. Tuzimski (Medical University of Lublin, Lublin, Poland)
  • Y. Vander Heyden (Free University of Brussels, Brussels, Belgium)
  • A. Voelkel (Poznań University of Technology, Poznań, Poland)
  • B. Walczak (University of Silesia, Katowice, Poland)
  • W. Wasiak (Adam Mickiewicz University, Poznań, Poland)
  • I.G. Zenkevich (St. Petersburg State University, St. Petersburg, Russian Federation)

 

KOWALSKA, TERESA
E-mail: kowalska@us.edu.pl

SAJEWICZ, MIECZYSLAW
E-mail:msajewic@us.edu.pl

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2021  
Web of Science  
Total Cites
WoS
652
Journal Impact Factor 2,011
Rank by Impact Factor Chemistry, Analytical 66/87
Impact Factor
without
Journal Self Cites
1,789
5 Year
Impact Factor
1,350
Journal Citation Indicator 0,40
Rank by Journal Citation Indicator Chemistry, Analytical 72/99
Scimago  
Scimago
H-index
29
Scimago
Journal Rank
0,27
Scimago Quartile Score Chemistry (miscellaneous) (Q3)
Scopus  
Scopus
Cite Score
2,8
Scopus
CIte Score Rank
General Chemistry 210/409 (Q3)
Scopus
SNIP
0,586

2020
 
Total Cites
650
WoS
Journal
Impact Factor
1,639
Rank by
Chemistry, Analytical 71/83 (Q4)
Impact Factor
 
Impact Factor
1,412
without
Journal Self Cites
5 Year
1,301
Impact Factor
Journal
0,34
Citation Indicator
 
Rank by Journal
Chemistry, Analytical 75/93 (Q4)
Citation Indicator
 
Citable
45
Items
Total
43
Articles
Total
2
Reviews
Scimago
28
H-index
Scimago
0,316
Journal Rank
Scimago
Chemistry (miscellaneous) Q3
Quartile Score
 
Scopus
393/181=2,2
Scite Score
 
Scopus
General Chemistry 215/398 (Q3)
Scite Score Rank
 
Scopus
0,560
SNIP
 
Days from
58
submission
 
to acceptance
 
Days from
68
acceptance
 
to publication
 
Acceptance
51%
Rate

2019  
Total Cites
WoS
495
Impact Factor 1,418
Impact Factor
without
Journal Self Cites
1,374
5 Year
Impact Factor
0,936
Immediacy
Index
0,460
Citable
Items
50
Total
Articles
50
Total
Reviews
0
Cited
Half-Life
6,2
Citing
Half-Life
8,3
Eigenfactor
Score
0,00048
Article Influence
Score
0,164
% Articles
in
Citable Items
100,00
Normalized
Eigenfactor
0,05895
Average
IF
Percentile
20,349
Scimago
H-index
26
Scimago
Journal Rank
0,255
Scopus
Scite Score
226/167=1,4
Scopus
Scite Score Rank
Chemistry (miscellaneous) 240/398 (Q3)
Scopus
SNIP
0,494
Acceptance
Rate
41%

 

Acta Chromatographica
Publication Model Online only
Gold Open Access
Submission Fee none
Article Processing Charge 400 EUR/article
Regional discounts on country of the funding agency World Bank Lower-middle-income economies: 50%
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Acta Chromatographica
Language English
Size A4
Year of
Foundation
1992
Volumes
per Year
1
Issues
per Year
4
Founder Institute of Chemistry, University of Silesia
Founder's
Address
PL-40-007 Katowice, Poland, Bankowa 12
Publisher Akadémiai Kiadó
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 2083-5736 (Online)

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