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  • 1 Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt
  • | 2 Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, The British University in Egypt, 11837, El sherouk city, Egypt
Open access

Abstract

Sustainable chemistry established one of kind standards to maintain protection of environment through using safer mobile phase composition and/or lower solvent consumption. A fast green micellar HPLC method was developed and applied for the first time aiming at simultaneous determination of chlorpheniramine maleate, one of the most widely used antihistamine in combination with levochlopersatine fenodizoate or dextromethorphan hydrobromide or dexamethasone, in their pure forms, laboratory prepared mixtures and pharmaceutical dosage forms used in alleviating the symptoms of cough resulting from common colds and allergy. The separation was achieved on Kinetex C18 column (100 mm × 4.6 mm i.d., 2.6-μm particle size) using micellar aqueous mobile phase consisting of (30 mM sodium dodecyl sulfate and 50 mM sodium dihydrogen phosphate, pH 5) and ethanol (85:15) with UV detection at 230 nm. The four drugs were successfully separated using isocratic elution in a single run not exceeding 7 min. According to ICH guidelines, the method was confirmed to be linear, accurate and precise over the concentration ranges of 5–60 μg mL−1 for chlorpheniramine maleate, 10–100 μg mL−1 for levocloperastine fenodizoate and dextromethorphan hydrobromide and 5–30 μg mL−1 for dexamethasone. In addition, the greenness of the developed method was assessed using two different tools indicating their least hazardous effect on the environment.

Abstract

Sustainable chemistry established one of kind standards to maintain protection of environment through using safer mobile phase composition and/or lower solvent consumption. A fast green micellar HPLC method was developed and applied for the first time aiming at simultaneous determination of chlorpheniramine maleate, one of the most widely used antihistamine in combination with levochlopersatine fenodizoate or dextromethorphan hydrobromide or dexamethasone, in their pure forms, laboratory prepared mixtures and pharmaceutical dosage forms used in alleviating the symptoms of cough resulting from common colds and allergy. The separation was achieved on Kinetex C18 column (100 mm × 4.6 mm i.d., 2.6-μm particle size) using micellar aqueous mobile phase consisting of (30 mM sodium dodecyl sulfate and 50 mM sodium dihydrogen phosphate, pH 5) and ethanol (85:15) with UV detection at 230 nm. The four drugs were successfully separated using isocratic elution in a single run not exceeding 7 min. According to ICH guidelines, the method was confirmed to be linear, accurate and precise over the concentration ranges of 5–60 μg mL−1 for chlorpheniramine maleate, 10–100 μg mL−1 for levocloperastine fenodizoate and dextromethorphan hydrobromide and 5–30 μg mL−1 for dexamethasone. In addition, the greenness of the developed method was assessed using two different tools indicating their least hazardous effect on the environment.

1 Introduction

Most of analytical techniques lack safety due to hazardous solvents and toxic chemicals used. Thus, green chemistry attracted the attention of analytical chemists to develop analytical approaches that are safe to the environment and mankind. In the last few decades, Liquid chromatography was considered to be unsafe technique due to the use of some toxic and harmful solvents that may result in hazardous effects and adverse impact on the environment and analyst [1]. For these purposes, greening chromatography was investigated and became an urge to substitute hazardous solvents by eco-friendly alternates like water and ethanol [2]. Micellar liquid chromatography (MLC) is a technique supporting the concept of green chemistry and represents an excellent alternative to a traditional liquid chromatography. MLC has different advantages such as proficiency of separation of drugs with different nature and probability of improvement the efficiency and solvent strength [3].

Cough could be involuntary as a protective reflex action of the human body to clear and remove foreign substances and particles from the respiratory tract and passage of breathing. It may be acute due to different respiratory tract infections including common cold and flu, or chronic due to smoking and asthma. Cough is generally treated with some drug combinations [4]. Levocloperastine fendizoate, dextromethorphan hydrobromide and dexamethasone alone or in combination with antihistamines as chlorphenamine maleate are effective components used for treatment of cough resulting from common colds and allergy.

Chlorpheniramine maleate (CPM), [(3RS′)-3-(4-chloophenyl)-N, N-dimethyl-3-(pyridin-2-yl) propan-1-amine hydrogen (Z)-butenedioate] (Fig. 1), is one of the mostly used drugs for treatment of allergic conditions such as allergic rhinitis, hay fever, cough and the common cold. Levocloperastine fendizoate (LCF), 1-[2-[(S)-(4-chlorophenyl)-phenylmethoxy] ethyl] piperidine; 2-(4-hydroxy-3-phenylbenzoyl) benzoic acid (Fig. 1) is centrally acting cough suppressant. It also has some antihistaminic action [5]. It is combined with CPM as it acts on the cough center, without any depression of respiratory center in brain [6]. Dextromethorphan hydrobromide (DXM), [(+)-3-Methoxy-17-methyl-9, 13, 14-morphinan hydrobromide monohydrate] (Fig. 1), is centrally acting cough suppressant. In cough syrups, it is available mostly in combination with sedating anti-histamine CPM [5]. Dexamethasone (DEX), [9-fluoro-11β, 17, 21-trihydroxy-16α-methylpregna-1, 4-diene, 3, 20-dione] (Fig. 1) is a corticosteroid anti-inflammatory agent. CPM and DEX are formulated together in the local Egyptian market in the form of syrups for the relief of asthma [5].

Fig. 1.
Fig. 1.

Chemical structure of studied drugs

Citation: Acta Chromatographica 2021; 10.1556/1326.2021.00883

Literature review revealed that several methods have been carried out for the analysis of CPM, LCF, DXM, and DEX in their mixture or in their combination with other drugs. CPM and LCF were determined by HPLC method [6]. CPM and DXM were estimated by spectrophotometric methods [7, 8] and HPLC methods [9–19]. CPM and DEX were determined by spectrophotometric methods [20–23], spectrofluorometric method [24], HPLC methods [25–27], and TLC methods [27].

Moreover, a micellar liquid chromatography was developed for estimation of CPM in various samples including pharmaceutical formulation [28–30].

To the best of our knowledge, no reported micellar HPLC method has been developed previously for assay of these four drugs until now. Hence, the present research was proposed to introduce an eco-friendly simple and rapid micellar HPLC method for the first time to simultaneously estimate CPM in three combined dosage forms with LCF, DXM or DEX using single run in about 7 min. The mobile phase is eco-friendly containing low proportion of ethanol as an organic modifier with the objective of replacement hazardous solvents of the published articles without any sample extraction, pre-treatment filtration or derivatization steps. Moreover, the greenness of the developed method was assessed using analytical Eco-scale and the Green Analytical Procedure Index tools (GAPI).

2 Material and methodology

2.1 Materials and reagents

  1. -Chlorpheniramine maleate (CPM) with purity of 99.89% was obtained as a gift from Memphis Pharmaceutical Company, Cairo, Egypt.
  2. -Levocloperastine fendizoate (LCF) with purity of 99.92% was kindly supplied by Chemipharm Pharmaceutical Company, Cairo, Egypt.
  3. -Dextromethorphan hydrobromide (DXM) with purity of 99.84% was obtained as a gift from Kahira, Pharmaceutical Company, Cairo, Egypt.
  4. -Dexamethasone (DEX) with 99.86% purity was kindly provided by Amoun, Pharmaceutical Company, Cairo, Egypt.
  5. -Lupituss-CPM® syrup (each 5 mL contains 4 mg CPM and 20 mg LCF, B.N.M181259) a product of Lupin Ltd., Mumbai, India.
  6. -Codaphen-N® syrup (each 5 mL contains 1 mg CPM and 5 mg DXM, B.N.9226009) a product of Alexandria Pharmaceutical Company, Alexandria, Egypt
  7. -Apidone® syrup (each 5 mL contains 2 mg CPM and 0.5 mg DEX, B.N.190095) a product of Amoun Pharmaceutical Company, Cairo, Egypt.
  8. -Acetonitrile, methanol, ethanol, n-propanol, n-butanol, orthophosphoric acid, sodium dodecyl sulfate (SDS), and sodium dihydrogen phosphate were obtained from Sigma-Aldrich, Darmstadt, Germany. High purity distilled water was used in this study.

2.2 Instrumentation

Agilent 1100 HPLC system equipped with binary pump, micro vacuum degasser, thermostatic column compartment, and variable wavelength and UV detector. Sample injection was achieved using Agilent 1100 series autosampler. Data processing and acquisition was done by Agilent ChemStation software, version A.10.01 (Abbotta, USA). Analysis was performed on a Kinetex C 18 column (100 mm, 4.6 mm i.d., 2.6 μm); (Phenomenex, USA). Jenway digital pH- meter (Jenway, UK) was necessary for pH adjustment. Ultrasonic bath from BHA-180 T (Abbotta, USA) was used. The mobile phase was filtered through Charles Austen Pumps Ltd. Filter; model-B100 SE (England, UK) using 0.45 µm milli-pore filters (Gelman, Germany).

2.3 Chromatographic conditions

Kinetex C18 Column (100 × 4.6 mm i.d, 2.6 µm, 100 Å) (Phenomenex, USA) thermostatted at 25 ºC and micellar mobile phase consisted of 30 mM sodium dodecyl sulfate, 50 mM sodium dihydrogen phosphate, adjusted to pH 5 using orthophosphoric acid, and ethanol (85:15). The mobile phase was degassed by sonication for 15 min and filtered through 0.45-μm Millipore membrane filter before use. The separation was performed at a flow rate of 1.0 mL/min and UV detection at 230 nm.

2.4 Standard solutions

Stock solutions of 500 μg mL−1 of CPM, LCF, DXM, and DEX were individually prepared in methanol. All solutions were found to be stable for more than 1 week if stored at 4 °C, protected from light.

2.5 Construction of calibration curves

Concentrations ranging from 5–60 μg mL−1 of CPM, 10–100 μg mL−1 of LCF, DXM and 5–30 μg mL−1 of DEX were prepared by serial dilutions of aliquots of the stock solution with the mobile phase. These solutions were then analyzed by injecting into the chromatographic system and eluted with the mobile phase under the above described chromatographic conditions. The peak area was plotted against the corresponding concentrations to construct the calibration graphs; in addition, the linear regression equations were calculated.

2.6 Analysis of laboratory prepared mixtures

Aliquots of CPM in combination with LCF, DXM or DEX in different ratios were transferred into 10 mL volumetric flasks, completed to the volume with mobile phase and injected into the chromatographic system under the above described chromatographic conditions. The percent found for each drug was calculated based on calibration graphs or the derived regression equations.

2.7 Assay of Pharmaceutical dosage forms

Aliquots of Lupituss-CPM® Syrup equivalent to 4 mg of CPM and 20 mg of LCF, Codaphen-N® syrup equivalent to 1 mg CPM and 5 mg DXM or Apidone® syrup equivalent to 2 mg CPM and 0.5 mg DEX were transferred to 100 mL volumetric flasks, completed to the volume with methanol, mixed well and filtered. Different concentrations were analyzed by injecting into the chromatographic system as described before under construction of calibration curves.

3 Results and discussion

The main target of this work is to develop a new eco-friendly HPLC method for to determination of CPM in three combined dosage forms with LCF, DXM and DEX with good resolution and minimum analysis time. Micellar liquid Chromatography (MLC) analysis meets the requirements of green chemistry by using environment-friendly reagents and have lower impact on environmental and less hazardous effect compared to conventional chromatographic separation techniques. Moreover, it can be used to solve problems of separation of drugs which differ in their polarity in presence of low percent of organic modifier. The separation was achieved due to the existence of various types of interactions of the analytes with micelles in the mobile phase and the column surface altered by the adsorption of surfactant molecules, e.g., electrostatic, hydrophobic and steric interactions, permitting the separation of compounds of different nature [31].

The optimization of chromatographic conditions to allow the optimum separation of the four studied drugs with symmetrical peaks were studied. Figure 2 illustrates a typical chromatogram for the analysis of a synthetic mixture of CPM, LCF, DXM and DEX under the above described optimum chromatographic conditions.

Fig. 2.
Fig. 2.

Typical chromatogram of a synthetic mixture of CPM (30 µg/mL), LCF (50 µg/mL), DXM (50 µg/mL) and DEX (20 µg/mL) using micellar aqueous mobile phase consisting of (30 mM sodium dodecyl sulfate and 50 mM sodium dihydrogen phosphate, pH 5) and ethanol (85:15)

Citation: Acta Chromatographica 2021; 10.1556/1326.2021.00883

3.1 Method development

3.1.1 Choice of column

Three different columns were studied including: Kinetex C18 Column (100 × 4.6 mm i.d, 2.6 µm), Equisil ODS C18 Column (150 × 4.0 mm i.d, 5 µm) and Shim-pack CLC-C8 column (150 × 4.6 mm i.d, 5 μm); The first column was the most appropriate one which gave symmetrical, well defined peaks with minimum retention time. While, the use of Equisil ODS C18 Column, only DXM and LCF were separated. One the other hand, usage of Shim-pack CLC-C8 column; overlapping peaks were observed with longer retention times.

3.1.2 Choice of detection wavelength

Different wavelengths were tried in order to find the most suitable one for the analysis including 210, 220, 230, 240 and 250 nm. The most suitable wavelength was found to be 230 nm showing the best sensitivity detection of the four drugs.

3.1.3 Effect of mobile phase composition

Various mobile phases were evaluated by using different proportions of SDS and organic modifiers. The effect of changing the concentration of SDS on the retention times and separation of the four drugs was tested over the range 10–100 mM. It was found that 30 mM SDS was the most suitable one giving higher number of theoretical plates and best resolution; Table 1. Different organic modifier was tried in order to achieve the best separation between the four drugs in a short run time such as ethanol, methanol, acetonitrile, n-butanol and n-propanol. In case of using methanol, it failed in separation of four drugs in which CPM wasn't separated. Acetonitrile caused separation of DXM and DEX only with broad peak. N-butanol allowed separation of mixture with very poor sensitivity and longer retention time for CPM, DXM, and DEX. N-propanol caused overlapped peaks of four drugs. It was found that ethanol resulted in better separation and improvement in the peak shape. The effect of the amount of ethanol was examined from 5 to 20%; using 15% ethanol gave good resolution and symmetrical peak in adequate time as shown in Table 1.

Table 1.

Optimization of chromatographic conditions for the determination of studied drugs by the proposed micellar HPLC method

3.1.4 Effect of buffer concentration and pH

Three different concentrations of sodium dihydrogen phosphate buffer were tried. The most suitable concentration was found to be 50 mM giving symmetrical, efficiently-separated and well-resolved peaks. Different pH values (4.0–6.0) were tried to investigate their effect on the separation; the number of theoretical plates increased reaching its highest value at pH 5.0. So, pH 5.0 was selected as it led to well-resolved symmetrical peak and better resolution of four analytes (Table 1).

3.1.5 Effect of column temperature and flow rate

The effect of column temperature was studied from 25 to 40 °C. The retention of four drugs were decreased at higher temperature with increased the tailing factor. Thus, the optimal temperature was chosen to be 25 °C to give best resolution and best peak shape. In addition, the influence of the flow rate on the separation of the drug was also examined. At a flow rate 1.0 mL min−1; good separation with minimum retention time (Table 1).

3.2 Method validation

International conference of Harmonization (ICH) guidelines [32] was followed to validate the proposed method.

3.2.1 Linearity

Under the above suggested experimental conditions, calibration curves relating the obtained peak areas to the corresponding concentrations of the drugs were found to be linear over the ranges of 50–60 μg mL−1 for CPM, 10–100 μg mL−1 for LCF and DXM and 5–30 μg mL−1 for DEX. The regression equations and regression parameters were obtained (Table 2).

Table 2.

Analytical performance data for the determination of the studied drugs by the proposed micellar HPLC method

ParametersCPMLCFDXMDEX
Linearity range ( μg mL−1)5–6010–10010–1005–30
Regression equation
 A = a+bc
 Slope (b) ± SD6.935 ± 0.02710.871 ± 0.0709.671 ± 0.0535.659 ± 0.043
Intercept (a) ± SD0.220 ± 0.9030.439 ± 4.2540.613 ± 3.2000.595 ± 0.829
SD of residuals1.2415.4674.1260.891
Correlation Coefficient (r)0.99990.99980.99990.9998
LOD (μg mL−1)0.431.291.090.48
LOQ (μg mL−1)1.303.913.311.47

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

Sensitivity of the proposed methods were evaluated and stated based on LOD (3.3 SD/S) and LOQ (10 SD/S), Where SD is the standard deviation of multiple blank samples and S is the slope of calibration curve of the drug (Table 2).

3.2.3 Accuracy and precision

The accuracy of the proposed method was tested by comparing the results with the comparison methods [6, 19, 27]. No significant difference between them regarding the accuracy and precision, respectively, as mentioned by Statistical analysis of the data [33] (Table 3). Repeatability and intermediate precision were evaluated, and the results are summarized in Table 4. The values for the RSD% were less than 2 units, indicating good precision of the proposed method.

Table 3.

Application of the proposed micellar HPLC method for the determination of the studied drugs in pure form

DrugProposed methodComparison methods [6, 19, 27]
Conc. added (μg mL−1)Found* (μg mL−1)% RecoveryTaken (μg mL−1)Found* (μg mL−1)% Recovery
CPM54.9899.641010.04100.44
109.9499.492019.9199.56
2020.03100.183030.04100.15
3029.8799.57
4040.29100.74
6059.8699.77
Mean% ± SD99.90 ± 0.48100.05 ± 0.45
t-test0.46 (2.36)
F-test1.14 (19.29)
LCF1010.02100.27109.8698.63
2019.8199.082020.27101.36
4040.61101.533029.8699.55
6059.6699.45
8079.4499.31
100100.43100.43
Mean% ± SD100.01 ± 0.9299.85 ± 1.39
t-test0.21(2.36)
F-test2.28(19.29)
DXM109.9999.915050.31100.62
2019.9899.937574.3899.18
4040.02100.05100100.31100.31
6059.6699.45
8080.69100.87
10099.6399.64
Mean% ± SD99.98 ± 0.49100.04 ± 0.76
t-test0.15(2.36)
F-test2.41(19.29)
DEX55.11102.2755.09101.80
109.8898.833029.7599.15
1515.09100.635050.14100.28
2019.7698.84
2525.08100.33
3030.05100.20
Mean% ± SD100.18 ± 1.28100.41 ± 1.33
t-test0.25(2.36)
F-test1.08(19.29)

*Average of three separate determinations.

The values between parentheses are the tabulated t and F values at P = 0.05 [32, 33].

Table 4.

Precision data for the determination of the studied drugs by the proposed micellar HPLC method

DrugTaken (μg mL−1)IntradayaInterdayb
Mean ± S.D.*Precision (RSD%)Mean ± S.D.*Precision (RSD%)
CPM1098.03 ± 0.810.8398.70 ± 0.470. 48
4098.41 ± 0.870.8898.84 ± 1.071.08
6097.66 ± 0.560.5798.68 ± 0.770.78
LCF10100.09 ± 1.331.33100.20 ± 1.801.80
5099.76 ± 1.921.9399.75 ± 1.551.55
100101.12 ± 1.341.33100.59 ± 1.441.43
DXM1099.40 ± 0.880.8999.63 ± 1.551.56
5099.69 ± 1.401.4099.59 ± 1.611.62
100100.18 ± 0.760.76100.30 ± 1.311.31
DEX10100.50 ± 1.441.4399.90 ± 1.671.67
20100.38 ± 0.630.63100.28 ± 0.830.83
30101.45 ± 1.511.49100.91 ± 1.461.45

*Average of three separate determinations.

a Within the day.

b Three consecutive days.

3.2.4 Selectivity

The selectivity of the method was calculated by the assay of different laboratory prepared mixtures of CPM and LCF, DXM, and DEX separately within the linearity range and good results were obtained. Acceptable results were obtained and summarized in (Table 5).

Table 5.

Determination of CPM in laboratory prepared mixtures with LCF, DXM and DEX by the proposed micellar HPLC method

Laboratory prepared mixtures (μg mL−1)Recovery%*Recovery%*Laboratory prepared mixtures (μg mL−1)Recovery%*
CPMLCF or DXMCPMLCFCPMDXMCPMDEXCPMDEX
505099.78101.32101.02100.065599.89100.22
20100102.0398.22101.88102.34601598.19101.60
510101.4698.08100.16101.682010101.8398.17
402098.8299.68100.77101.981530101.2099.28
601298.9598.8998.12100.49520101.58100.43
Mean% ± SD100.24 ± 1.4699.24 ± 1.33100.39 ± 1.41101.31 ± 0.99100.54 ± 1.5199.94 ± 1.29

*Average of three separate determinations.

3.2.5 Robustness

The method verified to be robust by testing the effect of slight changes of pH of mobile phase (±0.1), flow rate (±0.1) and percent of ethanol (±1%). No significant effect was observed.

3.2.6 System suitability testing

The system suitability parameters were calculated according to guidelines of the United States Pharmacopeia (USP) [34] to ensure system performance during the analysis, where the system was found to be suitable. System suitability parameters were evaluated for the seven peaks (Table 6), and they were found satisfactory and within the reported acceptance criteria.

Table 6.

System suitability data for the proposed micellar HPLC method

ParametersCPMLCFDXMDEXReference values
Number of theoretical plates (N)6238541446633569N>2000
Resolution factor (Rs)5.244.684.31>2
Selectivity factor (α)1.061.071.071≤
Capacity factor ( K´)3.323.122.923.131–10
Tailing factor (T)1.181.211.141.110.9–1.2

3.2.7 Application to pharmaceutical dosage forms

The method was utilized successfully for determination of CPM simultaneously in its combined dosage forms with LCF, DXM and DEX. The results were acceptable and revealed high accuracy and good agreement with the comparison methods [6, 19, 27] results as shown in Figs 35 and Table 7.

Fig. 3.
Fig. 3.

Micellar HPLC determination of CPM (5 µg/mL) and LCF (25 µg/mL) in Lupituss CPM® syrup using micellar aqueous mobile phase consisting of (30 mM sodium dodecyl sulfate and 50 mM sodium dihydrogen phosphate, pH 5) and ethanol (85:15)

Citation: Acta Chromatographica 2021; 10.1556/1326.2021.00883

Fig. 4.
Fig. 4.

Micellar HPLC determination of CPM (5µg/mL) and DXM (25 µg/mL) in Codaphen-N® syrup using micellar aqueous mobile phase consisting of (30 mM sodium dodecyl sulfate and 50 mM sodium dihydrogen phosphate, pH 5) and ethanol (85:15)

Citation: Acta Chromatographica 2021; 10.1556/1326.2021.00883

Fig. 5.
Fig. 5.

Micellar HPLC determination of CPM (20 µg/mL) and DEX (5 µg/mL) in Apidone® syrup using micellar aqueous mobile phase consisting of (30 mM sodium dodecyl sulfate and 50 mM sodium dihydrogen phosphate, pH 5) and ethanol (85:15)

Citation: Acta Chromatographica 2021; 10.1556/1326.2021.00883

Table 7.

Assay results for the determination of CPM in combined dosage forms with LCF, DXM and DEX

Dosage formProposed methodComparison methods [6, 19, 27]
Conc. taken (μg mL−1)% FoundConc. taken (μg mL−1)% Found
CPMLCFCPMLCFCPMLCFCPMLCF
Lupituss CPM® syrup525100.4299.86210101.3899.58
105099.1698.2452598.2499.56
2010098.07100.5963099.83100.78
Mean ± S.D.99.22 ± 1.1899.56 ± 1.2099.82 ± 1.5799.97 ± 0.71
t-test0.21(2.776)0.21(2.776)
F-test1.77(19)2.86(19)
CPMDXMCPMDXMCPMDXMCPMDXM
Codaphen-N® syrup52598.74100.25105098.64100.12
1050102.09100.22157598.9399.67
2010099.20101.202010099.6999.68
Mean ± S.D.100.01 ± 1.82100.56 ± 0.5599.09 ± 0.5499.82 ± 0.26
t-test0.34(2.776)0.86 (2.776)
F-test11.36(19)4.47 (19)
CPMDEXCPMDEXCPMDEXCPMDEX
Apidone® syrup20597.89101.9820599.63100.20
401099.16100.744010100.9899.19
601598.30100.119022.5101.2298.50
Mean ± S.D.98.45 ± 0.65100.94 ± 0.95100.61 ± 0.8699.29 ± 0.85
t-test1.42(2.776)0.92(2.776)
F-test1.75(19)1.25(19)

3.2.8 Comparison with other HPLC methods

The proposed green micellar chromatographic method is compared with other previously reported methods for determination of Chlorpheniramine in presence of other drugs used in treatment of cold in terms of composition of mobile phase, linearity range, LOD, LOQ, mixture, and total run time as shown in Table 8. It is obvious that the proposed method is the first one applied for simultaneous and rapid estimation of chlorpheniramine, levochlopersatine fenodizoate, dextromethorphan hydrobromide and dexamethasone in a single run which could allow the concurrent analysis of three different dosage forms at the same time using isocratic elution with simple mobile phase, ideal chromatographic peaks with high resolution and high sensitivity. Moreover, it uses a green ecofriendly solvent presenting no hazards to the environment and personnel replacing classically used organic solvents (i.e., acetonitrile and methanol) in other methods. Also, it displays wider linearity range for the four drugs in comparison to the previously reported methods with low limit of detection and quantification [6, 19, 27], and the total run time for the complete resolution of the four drugs is less than 7 minutes which is less than other reported micellar HPLC methods [28–30].

Table 8.

Comparison of the proposed micellar HPLC method with previously reported HPLC methods

MethodMobile phaseLinearity range (μg mL−1)LOD (μg mL−1)LOQ (μg mL−1)MixtureTotal run timeRef.
Micellar per aqueous liquid chromatographic method0.003 mol/L Brij-35 aqueous solution and 0.02 mol/L potassium dihydrogen phosphate: acetonitrile (96:4, v/v), pH 3.0.1.30–16.00 for CPM

5.22–83.20 for DXM
0.14 μg mL−1 for CPM

0.37 for DXM
0.86 for CPM

1.25 for DXM
Chlorpheniramine, pseudoephedrine hydrochloride, caffeine, paracetamol, dextromethorphan and diphenhydramine30 minutes28
Micellar electrokinetic chromatographysodium dihydrogenphosphate: 10 mM sodium tetraborate buffer (pH 9.0) containing 50 mM sodium dodecyl sulfate and acetonitrile (26% v/v)10–250 for CPM0.54Chlorpheniramine maleate and paracetamol in presence of other 7 cold remedies25.5 min29
Nonionic Micellar Liquid Chromatographic Method3.0 × 10−3 mol/L Brij-35 and 2.0 × 10−2 mol/L potassium dihydrogen phosphate): methanol (96:4, v/v), pH 30.80–1.70 for CPM0.170.57Chlorpheniramine maleate, paracetamol and pseudoephedrineLess than 9 minutes30
RP-HPLC Method10mM phosphate buffer Buffer (pH 6.5): Acetonitrile (50:50, % v/v)2.0–6.0 for CPM and 10.0–30.0 for LCF0.108 for CMP

0.496 for LCF
0.327 for CMP

1.504 for LCF
Chlorpheniramine maleate and Levocloperastine FendizoateLess than 7 minutes6
RP-HPLC MethodWater, pH 2: Acetonitrile (60:40, v/v)10–30 for CMP

50–100 for DXM
0.04 for CMP and 0.11 for DXM0.14 for CMP and 0.43 for DXMChlorpheniramine maleate and Dextromethorphan4 minutes19
RP-HPLC Method0.1 M ammonium acetate buffer: acetonitrile (60:40, v/v), pH 35–50  for DEX 2–90  for CPM1.03 for DEX

0.29 for CPM
3.14 for DEX

0.88 for CMP
Chlorpheniramine maleate and Dexamethasone in presence of Methyl and Propylparaben15 minutes27
Proposed method30 mM sodium dodecyl sulfate/50 mM sodium dihydrogen phosphate, pH 5 and ethanol (85:15, v/v)5–60 for CMP,

10–100 for LCF and DXM and 5–30 for DEX
0.43 for CMP

1.29 for LCF

1.09 for DXM

0.48 for DEX
1.30 for CMP

3.91 for LCF

3.31 for DXM

1.47 for DEX
Chlorpheniramine maleate, Levochlopersatine Fenodizoate, dextromethorphan hydrobromide and dexamethasoneLess than 7 minutes

3.3 Assessment of greenness of the proposed method

The greenness of the methods was evaluated according to the analytical eco-scale [35]. The result of analytical Eco-Scale analysis is the score that is calculated by subtracting penalty points from the basis of 100 points. The penalty points are assigned for high amounts and high hazards connected with utilization of chemicals, high energy consumption, occupational hazards and generation of wastes [36].

The penalty points of the proposed methods were; as shown in Table 9, which proves that the proposed method is an excellent green method of analysis. The green analytical procedure index is a new tool for the assessment of the green character for the entire analytical procedure; from the sample collection and passing through sample preservation, transport, preparation and then the final step of determination [37]. The GAPI evaluates using a pictogram with five colored pentagrams which represent each step of the procedure; there are color-scale with three levels; green for low, yellow for medium and red for high environmental impact. In general, the greater the number of steps involved in the procedure, the less the greenness as there will be an increased in the energy consumption and the volume of waste produced. For the first step of sample collection; this is the time delay between the sampling and the determination step [38]. The green assessment for the proposed method and other comparison methods using the GAPI tool, are illustrated in Fig. 6 and indicated the highest greenness of the suggested method. So, it can be used for routine analysis of the studied mixtures without harming the environment.

Table 9.

The penalty points of the proposed micellar HPLC method according to analytical. Eco-Scale

Reagents/InstrumentsPenalty points
SDS0
Ethanol0
Sodium dihydrogen phosphate0
HPLC0
Occupational hazards0
Waste5
Total ppsƩ5
Eco-scale95
Excellent green analysis
Fig. 6.
Fig. 6.

The green assessment profile for the proposed micellar HPLC and the comparison methods, using the GAPI tool

Citation: Acta Chromatographica 2021; 10.1556/1326.2021.00883

4 Conclusion

The green chemistry has challenged researchers and analysts in all fields to take in consideration the environmental impact of the entirety of their chemical procedures and to assess the greenness of their processes. In this work, we focused on replacing the toxic solvents commonly used, mainly acetonitrile and methanol, with more benign alternative solvents. The most promising green solvent is an ethanol as a green organic solvent in the mobile phase. Consequently, the developed method is the first eco-friendly simple and rapid micellar HPLC method for simultaneous determination of CPM in three combined dosage forms with LCF, DXM, or DEX using isocratic elution with a single run and short time. Moreover, the use of micellar mobile phase has advantages such as non-toxicity, no inflammability, and biodegradability. The proposed method was compared to other previously published methods for assessing their greenness and found more favorable for greener analysis. The ease and availability of the required solvents and instruments in addition to decreasing the organic solvent ratio indicate its reliability and allow its application in quality control laboratories.

Rerferences

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    Rashed, N.S.; Zayed, S.; Abdelazeem, A.; Fouad, F. Development and validation of a green HPLC method for the analysis of clorsulon, albendazole, triclabendazole and ivermectin using monolithic column: assessment of the greenness of the proposed method. Microchem. J. 2020, 157, 105069.

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    Sagathiya, K.; Bagada, H. Development and validation of RP-HPLC and HPTLC method of analysis for simultaneous estimation of ambroxol HCL, Dextromethorphan HBR and Guaifenesin in pharmaceutical cough cold preparation and statistical comparison of developed methods. Int. J. Pharm. Pharm. Sci. 2014, 6, 312316.

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    Wanjari, D.B.; Parashar, V.V.; Lulay, S.N.; Tajne, M.R.; Gaikwad, N.J. Simultaneous HPLC estimation of acetaminophen, chlopheniramine maleate, dextromethorphan hydrobromide and pseudoephedrine hydrochloride in tablets. Indian J. Pharm. Sci. 2004, 66(3), 345347.

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    Heydari, R. A New HPLC method for the simultaneous determination of acetaminophen, phenylephrine, dextromethorphan, chlorpheniramine in pharmaceutical formulation. Anal. Lett. 2008, 41(1), 965976.

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    Khalode, K.D.; Waiker, S.B.; Padmane, S.P. A Validated RP-HPLC Method for the simultaneous estimation of dextromethorphan hydrobromide and chlorpheniramine maleate in syrup formulation. Am. J. Pharm. Tech. Res. 2012, 2, 392394.

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    Goyal, T. A novel stability indicating HPLC methods for simultaneous estimation of guaiphensein, chlorpheniramine maleate and dextromethorphan HBr. IJPSR 2013, 4(11), 44354441.

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    Kapildev, R.J. Analytical method development and validaton of RP-HPLC for simultaneously estimation of chlorpheniramine maleate, dextromethorphen hydro-bromide, phenylephrine hydrochloride in cough syrup. IRAJ 2016, 4(1), 5358.

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    Jain, V.; Sharma, M.C. Validated RP-HPLC method for determining the levels of bromhexine HCl, chlorpheniramine maleate, dextromethorphan HBr and guaiphenesin in their pharmaceutical dosage forms. J. Taibah. Univ. Sci. 2016, 10(1), 3845.

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    • Search Google Scholar
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    Gyanendra, P.; Palled, M.S.; Bhat, A. R.; Gyanendra, P.S.; Aruna, M. Analytical method development and validation of acetaminophen, caffeine, phenylephrine hydrochloride, dextromethorphan hydrobromide and chlorpheniramine Maleate in tablet dosage form by RP- HPLC. Int. J. Pharm. Res. 2017, 1, 1013.

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  • 17.

    Kumar, M. S.; Shanmugapandiyan, P. RP-HPLC-PDA method for the simultaneous determination of phenylepherine, chlorpheneramine, paracetamol and dextromethorphan in bulk and marketed formulation. J. Pharm. Res. 2017, 11(2), 306312.

    • Search Google Scholar
    • Export Citation
  • 18.

    Din, N.U.; Shafi, H.; Imran, M.; Sarwar, M.; Tahir, M.A.; Khursheed, S. Validated reversed-phase liquid chromatographic method for simultaneous determination of dextromethorphan and chlorpheniramine in non-biological and biological matrices using PDA detector. Pharm. Anal. Acta 2018, 9(7), 16.

    • Search Google Scholar
    • Export Citation
  • 19.

    Sirigiri, B.; Chengalva, P.; Parameswari, S. A.; Aruna, G. Novel HPLC methods for simultaneous determination of chlorpheniramine maleate and dextromethorphan in bulk and pharmaceutical formulation. IJPSR 2018, 9(3), 11471151.

    • Search Google Scholar
    • Export Citation
  • 20.

    El-Yazbi, F. A.; Korany, M.; Abdel-Razak, O.; Elsayed, M. Derivative spectrophotometric determination of some corticosteroids in combinations with other drugs. J. Assoc. Offic. Anal. Chem. 1986, 69(4), 614618.

    • Search Google Scholar
    • Export Citation
  • 21.

    Goicoechea, H.C.; Collado, M.S.; Satuf, M.L.; Olivieri, A. C. Complementary use of partial least-squares and artificial neural networks for the non-linear spectrophotometric analysis of pharmaceutical samples. Anal. Bioanal. Chem. 2002, 374(3), 460465.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Darwish, H. W.; Metwally, F. H.; El Bayoumi, A. Discrete wavelet transform-partial least squares versus derivative ratio spectrophotometry for simultaneous determination of chlorpheniramine maleate and dexamethasone in the presence of parabens in pharmaceutical dosage form. Trop. J. Pharm. Res. 2015, 14(5), 859867.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Darwish, H.W.; Metwally, F. H.; El Bayoumi, A. Development of three methods for simultaneous quantitative determination of chlorpheniramine maleate and dexamethasone in the presence of parabens in oral liquids. Trop. J. Pharm. Res. 2015, 14(1), 153161.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    El-Yazbi, F.A.; Hammud, H. H.; Assi, S.A. New spectrofluorometric application for the determination of ternary mixtures of drugs. Anal. Chim. Acta 2006, 580(1), 3946.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Hattori, T.; Washio, Y.; Kamiya, N.; Itoh, Y.; Inoue, M. High performance liquid chromatographic analysis of drugs. I. Simultaneous determination of dexamethasone and chlorpheniramine maleate in ointment. J. Pharm. Soc. Jpn. 1979, 99(5), 537539.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Moyano, M. A.; Rosasco, M. A.; Pizzorno, M.T.; Segall, A.I. Simultaneous determination of chlorpheniramine maleate and dexamethasone in a tablet dosage form by liquid chromatography. J. AOAC Int. 2005, 88(6), 16771683.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Farid, N.F.; Naguib, I. A.; Moatamed, R. S.; El Ghobashy, M. R. TLC-Densitometric and RP-HPLC methods for simultaneous determination of dexamethasone and chlorpheniramine maleate in the presence of methylparaben and propylparaben. J. AOAC Int. 2017, 100(1), 5158.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Duan, X.; Liu, X.; Dong, Y.; Zhang, J.; He, S.H.; Uhagaze, S. A micellar HPLC simultaneous determination of six active ingredients in cold compound preparations. J. Liq. Chrom. Relat. Technol. 2019, 42(15-16), 485493.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Suntornsuk, L.; Pipitharome, O.; Wilairat, P. Simultaneous determination of paracetamol and chlorpheniramine maleate by micellar electrokinetic chromatography. J. Pharm. Biomed. Anal. 2003, 33, 441449.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30.

    Dong, Y.; Li, N.; An, O.; Lu, N. A novel nonionic micellar liquid chromatographic method for simultaneous determination of pseudoephedrine, paracetamol, and chlorpheniramine in cold compound preparations. J. Liq. Chromat. Rel. Tech. 2015 ,38, 251258.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Eid, M.; El-Shabrawy, Y.; El-Shaheny, R. Green micellar HPLC analysis of three angiotensin-converting enzyme inhibitors in their mixtures with hydrochlorothiazide and modeling of their retention behavior by fitting to Foley's model. J. Sep. Sci. 2017, 40(18), 36463654.

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    • Search Google Scholar
    • Export Citation
  • 32.

    ICH, Guidelines. Technical requirements for the registration of pharmaceutical for human use, validation of analytical procedures: text and methodologyQ2 (R1); International Conference on harmonization: Geneva, Switzerland, 2005; pp 1112.

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    Miller, J.C.; Miller, J.N. Statistics and Chemometrics for Analytical Chemistry, 5th edition Pearson Education Limited, Harlow, 2005.

  • 34.

    United States Pharmacopeia, 38/National Formulary 33 US Pharmacopeial Convention, Inc, Rockville, MD, 2014.

  • 35.

    Gałuszka, A.; Konieczka, P.; Migaszewski, Z. M.; Namieśnik, J. Analytical Eco-Scale for assessing the greenness of analytical procedures. Trac. Trends Anal. Chem. 2012, 37, 6172.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36.

    Tobiszewski, M.; Marc, M.; Galuszka, A.; Namiesnik, J. Green chemistry metrics with special reference to green analytical chemistry. Molecules 2015, 20, 1092810946.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37.

    Plotka-Wasylka, J.; A new tool for the evaluation of the analytical procedure: green analytical procedure index. Talanta 2018, 181, 204209.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Tobiszewski, M.; Mechlińska, A.; Namieśnik, J.; Green analytical chemistry–theory and practice. Chem. Soc. Rev. 2010, 39, 28692878.

  • 1.

    Mohamed, S.A.; Belal, F.F. A micellar HPLC method for simultaneous determination of methocarbamol in three different tablets using single run; application to human plasma and evaluation of the method greenness. Microchem. J. 2019, 148, 262269.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Rashed, N.S.; Zayed, S.; Abdelazeem, A.; Fouad, F. Development and validation of a green HPLC method for the analysis of clorsulon, albendazole, triclabendazole and ivermectin using monolithic column: assessment of the greenness of the proposed method. Microchem. J. 2020, 157, 105069.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    El-Shaheny, R.N.; El-Maghrabey, M.H.; Belal, F.F. Micellar liquid chromatography from green analysis perspective. Open Chem. 2015, 13(1), 877892.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Sagathiya, K.; Bagada, H. Development and validation of RP-HPLC and HPTLC method of analysis for simultaneous estimation of ambroxol HCL, Dextromethorphan HBR and Guaifenesin in pharmaceutical cough cold preparation and statistical comparison of developed methods. Int. J. Pharm. Pharm. Sci. 2014, 6, 312316.

    • Search Google Scholar
    • Export Citation
  • 5.

    Martindale, The Complete Drug Reference, 36th edn, The Pharmaceutical Press, London, 2014.

  • 6.

    Sharma, B.; Satone, D.; Pradhan, P.; Jain, H.; Meshram, H. Development and validation of RP-HPLC method for simultaneous estimation of levocloperastine fendizoate and chlorpheniramine maleate in their combined dosage form. Austin. J. Anal. Pharm. Chem. 2017, 4(2), 10831090.

    • Search Google Scholar
    • Export Citation
  • 7.

    Murtha, J.L.; Julian, T.N.; Radebaugh, G.W. Simultaneous determination of pseudoephedrine hydrochloride, chlorpheniramine maleate, and dextromethorphan hydrobromide by second-derivative photodiode array spectroscopy. J. Pharm. Sci. 1988, 77(8), 715718.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Khalode, K.D.; Waikar, S.B.; Padmane, S.P. A validated UV spectrophotometric method for simultaneous estimation of dextromethorphan hydrobromide and chlorpheniramine maleate in syrup formulation. IJPT 2012, 4(3), 46904699.

    • Search Google Scholar
    • Export Citation
  • 9.

    Gupta, N.D.; Heble, A.R. Quantitation of acetaminophen, chlorpheniramine maleate, dextromethorphan hydrobromide, and phenylpropanolamine hydrochloride in combination using high-performance liquid chromatograph. J. Pharm. Sci. 1984, 73(11), 15531556.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Wanjari, D.B.; Parashar, V.V.; Lulay, S.N.; Tajne, M.R.; Gaikwad, N.J. Simultaneous HPLC estimation of acetaminophen, chlopheniramine maleate, dextromethorphan hydrobromide and pseudoephedrine hydrochloride in tablets. Indian J. Pharm. Sci. 2004, 66(3), 345347.

    • Search Google Scholar
    • Export Citation
  • 11.

    Heydari, R. A New HPLC method for the simultaneous determination of acetaminophen, phenylephrine, dextromethorphan, chlorpheniramine in pharmaceutical formulation. Anal. Lett. 2008, 41(1), 965976.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Khalode, K.D.; Waiker, S.B.; Padmane, S.P. A Validated RP-HPLC Method for the simultaneous estimation of dextromethorphan hydrobromide and chlorpheniramine maleate in syrup formulation. Am. J. Pharm. Tech. Res. 2012, 2, 392394.

    • Search Google Scholar
    • Export Citation
  • 13.

    Goyal, T. A novel stability indicating HPLC methods for simultaneous estimation of guaiphensein, chlorpheniramine maleate and dextromethorphan HBr. IJPSR 2013, 4(11), 44354441.

    • Search Google Scholar
    • Export Citation
  • 14.

    Kapildev, R.J. Analytical method development and validaton of RP-HPLC for simultaneously estimation of chlorpheniramine maleate, dextromethorphen hydro-bromide, phenylephrine hydrochloride in cough syrup. IRAJ 2016, 4(1), 5358.

    • Search Google Scholar
    • Export Citation
  • 15.

    Jain, V.; Sharma, M.C. Validated RP-HPLC method for determining the levels of bromhexine HCl, chlorpheniramine maleate, dextromethorphan HBr and guaiphenesin in their pharmaceutical dosage forms. J. Taibah. Univ. Sci. 2016, 10(1), 3845.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Gyanendra, P.; Palled, M.S.; Bhat, A. R.; Gyanendra, P.S.; Aruna, M. Analytical method development and validation of acetaminophen, caffeine, phenylephrine hydrochloride, dextromethorphan hydrobromide and chlorpheniramine Maleate in tablet dosage form by RP- HPLC. Int. J. Pharm. Res. 2017, 1, 1013.

    • Search Google Scholar
    • Export Citation
  • 17.

    Kumar, M. S.; Shanmugapandiyan, P. RP-HPLC-PDA method for the simultaneous determination of phenylepherine, chlorpheneramine, paracetamol and dextromethorphan in bulk and marketed formulation. J. Pharm. Res. 2017, 11(2), 306312.

    • Search Google Scholar
    • Export Citation
  • 18.

    Din, N.U.; Shafi, H.; Imran, M.; Sarwar, M.; Tahir, M.A.; Khursheed, S. Validated reversed-phase liquid chromatographic method for simultaneous determination of dextromethorphan and chlorpheniramine in non-biological and biological matrices using PDA detector. Pharm. Anal. Acta 2018, 9(7), 16.

    • Search Google Scholar
    • Export Citation
  • 19.

    Sirigiri, B.; Chengalva, P.; Parameswari, S. A.; Aruna, G. Novel HPLC methods for simultaneous determination of chlorpheniramine maleate and dextromethorphan in bulk and pharmaceutical formulation. IJPSR 2018, 9(3), 11471151.

    • Search Google Scholar
    • Export Citation
  • 20.

    El-Yazbi, F. A.; Korany, M.; Abdel-Razak, O.; Elsayed, M. Derivative spectrophotometric determination of some corticosteroids in combinations with other drugs. J. Assoc. Offic. Anal. Chem. 1986, 69(4), 614618.

    • Search Google Scholar
    • Export Citation
  • 21.

    Goicoechea, H.C.; Collado, M.S.; Satuf, M.L.; Olivieri, A. C. Complementary use of partial least-squares and artificial neural networks for the non-linear spectrophotometric analysis of pharmaceutical samples. Anal. Bioanal. Chem. 2002, 374(3), 460465.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Darwish, H. W.; Metwally, F. H.; El Bayoumi, A. Discrete wavelet transform-partial least squares versus derivative ratio spectrophotometry for simultaneous determination of chlorpheniramine maleate and dexamethasone in the presence of parabens in pharmaceutical dosage form. Trop. J. Pharm. Res. 2015, 14(5), 859867.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Darwish, H.W.; Metwally, F. H.; El Bayoumi, A. Development of three methods for simultaneous quantitative determination of chlorpheniramine maleate and dexamethasone in the presence of parabens in oral liquids. Trop. J. Pharm. Res. 2015, 14(1), 153161.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    El-Yazbi, F.A.; Hammud, H. H.; Assi, S.A. New spectrofluorometric application for the determination of ternary mixtures of drugs. Anal. Chim. Acta 2006, 580(1), 3946.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Hattori, T.; Washio, Y.; Kamiya, N.; Itoh, Y.; Inoue, M. High performance liquid chromatographic analysis of drugs. I. Simultaneous determination of dexamethasone and chlorpheniramine maleate in ointment. J. Pharm. Soc. Jpn. 1979, 99(5), 537539.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Moyano, M. A.; Rosasco, M. A.; Pizzorno, M.T.; Segall, A.I. Simultaneous determination of chlorpheniramine maleate and dexamethasone in a tablet dosage form by liquid chromatography. J. AOAC Int. 2005, 88(6), 16771683.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Farid, N.F.; Naguib, I. A.; Moatamed, R. S.; El Ghobashy, M. R. TLC-Densitometric and RP-HPLC methods for simultaneous determination of dexamethasone and chlorpheniramine maleate in the presence of methylparaben and propylparaben. J. AOAC Int. 2017, 100(1), 5158.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Duan, X.; Liu, X.; Dong, Y.; Zhang, J.; He, S.H.; Uhagaze, S. A micellar HPLC simultaneous determination of six active ingredients in cold compound preparations. J. Liq. Chrom. Relat. Technol. 2019, 42(15-16), 485493.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Suntornsuk, L.; Pipitharome, O.; Wilairat, P. Simultaneous determination of paracetamol and chlorpheniramine maleate by micellar electrokinetic chromatography. J. Pharm. Biomed. Anal. 2003, 33, 441449.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30.

    Dong, Y.; Li, N.; An, O.; Lu, N. A novel nonionic micellar liquid chromatographic method for simultaneous determination of pseudoephedrine, paracetamol, and chlorpheniramine in cold compound preparations. J. Liq. Chromat. Rel. Tech. 2015 ,38, 251258.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Eid, M.; El-Shabrawy, Y.; El-Shaheny, R. Green micellar HPLC analysis of three angiotensin-converting enzyme inhibitors in their mixtures with hydrochlorothiazide and modeling of their retention behavior by fitting to Foley's model. J. Sep. Sci. 2017, 40(18), 36463654.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32.

    ICH, Guidelines. Technical requirements for the registration of pharmaceutical for human use, validation of analytical procedures: text and methodologyQ2 (R1); International Conference on harmonization: Geneva, Switzerland, 2005; pp 1112.

    • Search Google Scholar
    • Export Citation
  • 33.

    Miller, J.C.; Miller, J.N. Statistics and Chemometrics for Analytical Chemistry, 5th edition Pearson Education Limited, Harlow, 2005.

  • 34.

    United States Pharmacopeia, 38/National Formulary 33 US Pharmacopeial Convention, Inc, Rockville, MD, 2014.

  • 35.

    Gałuszka, A.; Konieczka, P.; Migaszewski, Z. M.; Namieśnik, J. Analytical Eco-Scale for assessing the greenness of analytical procedures. Trac. Trends Anal. Chem. 2012, 37, 6172.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36.

    Tobiszewski, M.; Marc, M.; Galuszka, A.; Namiesnik, J. Green chemistry metrics with special reference to green analytical chemistry. Molecules 2015, 20, 1092810946.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37.

    Plotka-Wasylka, J.; A new tool for the evaluation of the analytical procedure: green analytical procedure index. Talanta 2018, 181, 204209.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Tobiszewski, M.; Mechlińska, A.; Namieśnik, J.; Green analytical chemistry–theory and practice. Chem. Soc. Rev. 2010, 39, 28692878.

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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)
K. Kaczmarski (Rzeszow University of Technology, Rzeszów, Poland)
H. Kalász (Semmelweis University, Budapest, Hungary)
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)
J. Sherma (Lafayette College, Easton, PA, USA)
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)

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

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

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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
sumbission
 
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%
World Bank Low-income economies: 100%
Further Discounts Editorial Board / Advisory Board members: 50%
Corresponding authors, affiliated to an EISZ member institution subscribing to the journal package of Akadémiai Kiadó: 100%
Subscription Information Gold Open Access
Purchase per Title  

Acta Chromatographica
Language English
Size A4
Year of
Foundation
1992
Publication
Programme
2021 Volume 33
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 0236-6290 (Print)
ISSN 2083-5736 (Online)

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Feb 2021 0 0 0
Mar 2021 0 0 0
Apr 2021 0 0 0
May 2021 0 55 31
Jun 2021 0 144 91
Jul 2021 0 77 41
Aug 2021 0 6 2