Author:
Mona M. Abdel MoneimDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt

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Abstract

Muscle relaxants and pain killers with their different types are widely used as combination approach for treatment of pain associated with several muscle spasm conditions. A sensitive and simple HPLC-UV detection method was developed in this work for simultaneous assay of Dantrolene (DNT) and co-administrated: Ibuprofen (IBU) and Diclofenac (DIC). After simple protein precipitation, separation was achieved using C18 column (150 × 4.6 mm) with a mobile phase of acidified water with orthophosphoric acid (pH = 3.5) and acetonitrile using gradient elution with a flow rate of 1 mL/min. The DAD was adjusted at 380, 219, 280 and 240 nm to measure DNT, IBU, DIC, and dexamethasone (internal standard), respectively. Linearity was demonstrated over the range from 0.1 to 3 μg/mL, 1 to 40 μg/mL, and 0.1 to 2 μg/mL for DNT, IBU, and DIC, respectively. The validated method was applied successfully to compare the effect of co-administration of IBU or DIC on the pharmacokinetic profile of DNT.

Abstract

Muscle relaxants and pain killers with their different types are widely used as combination approach for treatment of pain associated with several muscle spasm conditions. A sensitive and simple HPLC-UV detection method was developed in this work for simultaneous assay of Dantrolene (DNT) and co-administrated: Ibuprofen (IBU) and Diclofenac (DIC). After simple protein precipitation, separation was achieved using C18 column (150 × 4.6 mm) with a mobile phase of acidified water with orthophosphoric acid (pH = 3.5) and acetonitrile using gradient elution with a flow rate of 1 mL/min. The DAD was adjusted at 380, 219, 280 and 240 nm to measure DNT, IBU, DIC, and dexamethasone (internal standard), respectively. Linearity was demonstrated over the range from 0.1 to 3 μg/mL, 1 to 40 μg/mL, and 0.1 to 2 μg/mL for DNT, IBU, and DIC, respectively. The validated method was applied successfully to compare the effect of co-administration of IBU or DIC on the pharmacokinetic profile of DNT.

1 Introduction

Dantrolene (DNT, Fig. 1a), a hydantoin derivative, is a muscle relaxing agent acting specifically on skeletal muscles and can reduce muscular tone by interfering with calcium release from sarcoplasmic reticulum [1, 2]. It has become the only clinically available specific medication for malignant hyperthermia (MH), a disease that is triggered by volatile anesthetics and succinylcholine in susceptible individuals [2, 3].

Fig. 1.
Fig. 1.

Chemical structures of (a) Dantrolene (DNT), (b) Ibuprofen (IBU) and (c) Diclofenac (DIC)

Citation: Acta Chromatographica 2022; 10.1556/1326.2022.01089

Ibuprofen (IBU) (Fig. 1b); and diclofenac (DIC) (Fig. 1c), are non-steroidal drugs with anti-inflammatory and analgesic effects [4].

Muscle relaxants as DNT are widely co-administrated with “nonsteroidal anti-inflammatory drugs, NSAIDs” as IBU or DIC for treatment of musculoskeletal conditions and pains because of their additive effect and greater pain relief [1, 5, 6].

Oral DNT shows bioavailability up to 70%, and peak concentrations in blood are reached 3–6 h after ingestion. The half-life in human plasma is reported to be 5–9 hours and up to 12.1 ± 1.9 hours in some other reports [2, 7].

No enough study is available about DNT pharmacokinetic behavior especially that it is commonly prescribed with different pain killers [2]. Since, hyperkalemia can be increased when DIC or IBU is combined with DNT [8]. Thus, the relationship between the effect of IBU and DIC as two representative examples of different NSAIDs on the pharmacokinetics of DNT and its plasma concentration should be carefully studied.

Reported methods for DNT, DIC and IBU assay in different matrices include spectrophotometric [9–11], spectrofluorimetric [5, 12], densitometric [13, 14], voltammetric [1, 15, 16], capillary isotachophoresis [17] and chromatographic methods [18–23].

To date, no assays are available for determination of DNT with IBU or DIC in real plasma samples. Aim of our study is to simultaneously assay DNT with IBU or DIC in plasma while using dexamethasone (DEX) as internal standard. The used HPLC method was validated based on the “Food and Drug Administration, FDA” [24] and applied to samples from rats received the combined two drugs DNT/IBU or DIC to compare the changes occurred in the pharmacokinetic profile of DNT upon their co-administration.

The proposed method proved to be of excellent accuracy, precision, specificity, and sensitivity making this the first analytical tool that can be used for further pharmacokinetic interaction study between DNT and the two drugs under investigation.

2 Materials

Pharmaceutical grades of DNT (99.98%), IBU (99.95%), DIC (99.90%), and DEX (99.92%) were kindly supplied by Chemipharm pharmaceutical industries, EIPICO pharmaceutical industries company, Medizen Pharmaceutical Industries, and Kahira Pharmaceutical and Chemical Industries Company (all in Cairo, Egypt). HPLC-grade methanol and acetonitrile (Sigma-Aldrich Chemie GmbH, Buchs, Switzerland), orthophosphoric acid (BDH Laboratory Suppliers, Poole, England), and high purity double distilled water were used.

3 Instrumentation and chromatographic conditions

The analysis was performed using an Agilent 1200 HPLC system with a diode array detector (DAD). The separation was accomplished with a column “Interstil-ODS -3” (150 × 4.6 mm, 5 μm) at ambient temperature. The mobile phase was water acidified with orthophosphoric acid (pH adjusted to be 3.5) and acetonitrile; and the elution system used was gradient (as demonstrated in Table 1) with flow rate 1 mL/min. The injection volume was 20 μL. To measure each drug at its λmax, the DAD was set at 380, 219, 280 and 240 nm to measure DNT, IBU, DIC, and dexamethasone (DEX, internal standard), respectively.

Table 1.

Gradient elution system

Time (min)AcetonitrileAcidified water (pH = 3)
01783
21783
77030

4 Standard solutions and calibrators

Stock solutions of 1,000 μg/mL of DNT, IBU, DIC, and DEX were prepared by dissolving the appropriate amounts of reference standards into methanol. A working IS solution containing 100 μg/mL DEX dissolved in methanol was further prepared. The plasma samples were extracted by spiking 250 μL of rat plasma in series of glass test tubes with appropriate aliquots of diluted working solutions of DNT and IBU or DIC, to reach concentrations in the range of Table 2 after extraction, with 10 μL of IS working solution followed by 500 μL acetonitrile. The tubes were vortex mixed 2 min and centrifuged at 14,000 rpm (−4 °C) for 10 min. A 20 μL volume was then injected from the extracted layer in triplicate and chromatographed. The used standards for calibration were as follows: 0.1, 0.3, 0.5, 0.6, 1, and 3 μg/mL plasma for DNT, 1, 3, 10, 20, 30, and 40 μg/mL plasma for IBU and 0.1, 0.3, 0.6, 1, 1.5, and 2 μg/mL plasma for DIC, all with 4 μg/mL plasma DEX (IS). Quality controls were considered to be 0.1, 1 and 0.1 μg/mL “LLOQ: lower limit of quantitation”, 0.3, 3 and 0.3 μg/mL “LQC: low quality control”, 1, 10 and 1 μg/mL “MQC: medium quality control” and 3, 40 and 2 μg/mL “HQC: high quality control” for DNT, IBU and DIC, respectively.

Table 2.

System suitability parameters of the HPLC system used

MixtureAnalyteRetention time (Rt), minCapacity factor (k′)Selectivity (α)Resolution (Rs)Asymmetry (Af)Efficiency (plates m−1)
Mixture 1DNT8.702.801.202.170.9021,025
DEX (IS)9.453.131.125.570.927,056
IBU11.654.090.9518,785.12
Mixture 2DNT8.702.801.202.170.9021,025
DEX (IS)9.453.131.124.240.927,056
DIC11.253.911.0912,656.25

k′ (2−10), α > 1, Rs > 2, Af (0.8–1.2) and plates m−1 (>2000).

5 In vivo application of the proposed method

To perform the pharmacokinetic investigation, three groups of Sprague–Dawley male rats (n = 5, 200–300 g) were used. The day before drug administration, food was prevented overnight but with free access to water. Using oral gavage, the first group had oral administration of 10 mg/kg DNT, group two: 10 mg/kg DNT and 17.8 mg/kg IB and group three: 10 mg/kg DNT and 2 mg/kg DIC. From each group, blood samples were obtained in the following intervals {0.5; 1; 2; 3; 4; 5; 7; 8 and 10 h}. using retro-orbital sampling into tubes containing K3.EDTA to prevent coagulation. Plasma was separated by centrifugation [4,000 rpm, 15 min]. To ensure stability of the plasma samples till analysis time, they were kept at −20C.

6 Results and discussion

6.1 Chromatographic conditions

Several method parameters were optimized to develop a reliable HPLC method for simultaneous determination of DNT with IBU or DIC in human plasma.

The separation was tried on different columns such as C8 (250 × 4.6 mm, 5 μm), C18 (150 × 4.6 mm, 5 μm), and C18 (250 × 4.6 mm, 5 μm) to achieve the highest sensitivity and resolution in suitable analysis time. The C18 (150 × 4.6 mm, 5 μm) column gave symmetrical peaks for all drugs and IS, so it was chosen to perform the separation.

Several phases were tried to reach the optimum separation between the drugs. Both acetonitrile and methanol were attempted as organic modifiers. Methanol caused broadness in the shape of the peaks in addition to their late elution. Consequently, several ratios of acetonitrile were tried in attempt to achieve the required separation using an isocratic mode. It was noticed that increasing the acetonitrile ratio caused early elution of DNT peak interfering with plasma peaks and at lower ratio of acetonitrile, IBU and DIC peaks eluted after very long time. Thus, the only solution was using gradient mode. Different gradient systems were tried, the only satisfactory separation within reasonable acceptable time achieved with the system shown in Table 1.

Regarding the aqueous phase, high purity double distilled water was initially tried but it resulted in broad peaks with low symmetry and long retention times. Thus, phosphate buffer was used but it caused baseline distortion. Thus, the best solution was using acidified water to pH 3.5 to avoid using buffer but still reaching the required pH. Different pHs were tried, alkaline to neutral pHs showed peak broadening, which directed the analysis to acidic pH values for acceptable K’ values and avoidance of peak tailing. The chosen final pH was pH 3.5 as it gave best results in terms of peaks shape and symmetry for all studied drugs.

Different internal standards were tried but only DEX gave acceptable retention time in the proposed gradient system of the method and similar chemical behavior in addition to having the required extraction recovery.

Since there is a huge variation in the λmax of the concerned drugs under study, especially that DNT the main drug has λmax of 380 nm while IBU has λmax of 219 nm, so the DAD was time programmed to measure each drug at its maximum wavelength according to its retention time. However, the robustness and reproducibility of the time programming system was not satisfactory. Thus, the optimum solution was measuring each drug at its λmax separately which is a huge advantage of using a DAD to increase the sensitivity of each measured drug. Meanwhile, 219 nm (Fig. 2) was chosen to show the separation of the three drugs, yet not at their optimum sensitivity and the drugs were separated with acceptable system suitability parameters in the retention times mentioned in Table 2.

Fig. 2.
Fig. 2.

Typical HPLC chromatograms for (a) Plasma spiked with DNT, IBU and IS at the concentrations representing the LLOQ at 219 nm, and (b) Plasma spiked with DNT, DIC and IS at the concentrations representing the LLOQ at 219 nm and (c) blank plasma sample at 219 nm

Citation: Acta Chromatographica 2022; 10.1556/1326.2022.01089

This method had several advantages including the simple extraction procedure involved a simple protein precipitation with acetonitrile resulting in sharp and symmetrical peaks. Methanol and acetonitrile were tested as protein precipitating agents in different ratios to plasma. However, acetonitrile was superior giving clearer supernatant in the added amount with respect to plasma (2:1). Protein precipitation is a simple technique with small number of steps. It is also not time consuming and does not use large amounts of organic solvents. Yet, used in several studies to extract complex matrices and still achieving the required sensitivity.

6.2 Validation of the proposed methods

Validation was done according to the “FDA Bioanalytical Method Validation guidance” [23].

6.2.1 Linearity

Table 3 represents all regression data showing correlation coefficient values ≥ 0.999, high F values with low-significance F values which indicates acceptable linearity. The LLOQ values of the drugs were of enough sensitivity for their determination in rat plasma and conducting the pharmacokinetic study.

Table 3.

Parameters of regression for DNT/IBU or DIC determination by the proposed method

ParameterDNT (λmax = 380 nm)IBU (λmax = 219 nm)DIC (λmax = 280 nm)
Linearity range, (µg/mL)0.1–31–400.1–2
QL (µg/mL)0.090.060.1
DL (µg/mL)0.030.020.03
Intercept2.65 × 10−22.55 × 10−23.41 × 10−2
Slope0.174.20 × 10−32.59 × 10−2
Correlation coefficient, r0.99900.99910.9992
Standard deviation of intercept (Sa)4.89 × 10−32.64 × 10−36.11 × 10−4
Standard deviation of slope (Sb)3.66 × 10−31.08 × 10−45.85 × 10−4
Standard deviation of residuals (Sy/x)8.71 × 10−33.34 × 10−38.79 × 10−4
F2100.091520.841956.10
Significance F1.36 × 10−63.71 × 10−52.54 × 10−5

6.2.2 Accuracy and precision

Table 4 summarizes accuracy and precision evaluation results. In spiked rat plasma, accuracy and interday precision of three concerned drugs were evaluated on three different days, and also within the same day for intraday precision evaluation. The assessment was done at the four levels (n = 6) of Table 4.

Table 4.

Precision and accuracy assessment of the proposed method for determination of DNT/IBU or DIC in human plasma

ConcentrationTheoretical concentration (µg/mL)Intra-day (n = 6)Inter-day (n = 6)
Mean % Recovery ± %RSD%ErMean % Recovery ± %RSD%Er
DNT
LLOQ0.196.88 ± 1.22−3.1297.65 ± 1.02−2.35
LQC0.398.90 ± 1.23−1.1099.90 ± 1.55−0.10
MQC1101.73 ± 0.951.7399.23 ± 1.76−0.77
HQC3101.90 ± 1.011.90101.40 ± 1.751.40
IBU
LLOQ198.55 ± 1.05−1.4599.50 ± 1.09−0.50
LQC396.99 ± 1.29−3.01103.40 ± 1.853.40
MQC10101.30 ± 1.741.30102.79 ± 1.262.79
HQC4098.25 ± 1.12−1.75102.55 ± 0.982.55
DIC
LLOQ0.199.56 ± 1.60−0.4499.90 ± 1.33−0.10
LQC0.399.60 ± 1.24−0.40101.22 ± 1.671.22
MQC1100.45 ± 1.880.45101.99 ± 1.841.99
HQC2102.30 ± 1.352.3099.86 ± 2.01−0.14

6.2.3 Selectivity

The HPLC peak purity of all drugs was checked (Figs 3 and 4). The purity angle was within the purity threshold for all drugs. Overlaid spectra of DNT, IBU, DIC, and DEX across their peaks indicate the purity of the peaks in plasma samples (Fig. 3).

Fig. 3.
Fig. 3.

Overlaid spectra illustrating peak purity of (a) DNT, (b) IBU, (c) DIC and (d) DEX (IS) in plasma samples for the HPLC method

Citation: Acta Chromatographica 2022; 10.1556/1326.2022.01089

Fig. 4.
Fig. 4.

Calculated purity thresholds for (a) DNT, (b) IBU and (c) DIC peaks in plasma

Citation: Acta Chromatographica 2022; 10.1556/1326.2022.01089

No interfering peaks, throughout the analysis, were noticed in plasma samples. Also, blank plasma chromatogram at 219 nm shows no interference (Fig. 2).

6.2.4 Robustness

Method's robustness was confirmed by analyzing sample solutions of the three drugs (each drug at three different concentrations) while making deliberate changes mentioned in Table 5. No changes were seen on peak area, resolution or retention times.

Table 5.

Robustness assessment for the proposed method

Parameters testedHPLC method (n = 3)
DNTIBUDIC
RSD % of peak areasRt ± SDRSD % of peak areasRt ± SDRSD % of peak areasRt ± SD
1) Mobile phase ratio [±1% organic phase]0.698.66 ± 4.49 × 10−20.9011.66 ± 2.70 × 10−20.9411.24 ± 2.48 × 10−2
2) Flow rate [1 ± 0.1 mL/min]1.028.66 ± 6.03 × 10−20.7711.65 ± 5.18 × 10−20.9511.25 ± 7.00 × 10−3
3) Column temperature [25 °C ± 2 oC]0.458.79 ± 8.42 × 10−20.5911.64 ± 2.77 × 10−20.8311.29 ± 2.87 × 10−2
4) pH of the aqueous phase [3.5 ± 0.2]0.308.65 ± 4.23 × 10−20.2211.64 ± 1.91 × 10−20.3111.29 ± 2.87 × 10−2
5) λ (± 2 nm)0.928.65 ± 5.26 × 10−20.8611.64 ± 4.57 × 10−21.5011.27 ± 6.23 × 10−2

6.2.5 Matrix effect

Five different rat plasma blanks were analysed to ensure the selectivity of the method. As seen in Fig. 2, plasma constituents caused no interference with the three drugs’ peaks.

6.2.6 Recovery study

Recovery values of the four quality control levels of the three drugs and IS indicate the acceptable extraction ability of the protein precipitation procedure in the current study. All extraction recoveries were 100 ± 5% (by comparing peaks’ areas of standards with those of extracted plasma samples for the drugs) which indicates reliable determination of the concerned drugs in the rat plasma.

6.2.7 Stability studies of plasma samples

To assess short-term stability, LQC and HQC spiked samples of the three drugs were kept for 6 h at room temperature and to evaluate postpreparative stability, the spiked samples were subjected to 5 °C for 24 h. In addition, to assess the freeze–thaw stability, three freezes–thaw cycles were done and long-term stability was assessed by storing the samples for 45 days at −70 °C. All calculated % recoveries and RSD% were within acceptable limits as seen in Table 6.

Table 6.

Stability tests in plasma (n = 6)

StabilityQC samplesDNTIBUDIC
Mean % Recovery ± %RSD%ErMean % Recovery ± %RSD%ErMean % Recovery ± %RSD%Er
Short-term (25oC, 6 h)LQC97.05 ± 1.92−2.9598.32 ± 1.10−1.68101.50 ± 1.981.50
HQC98.25 ± 1.60−1.75102.85 ± 1.652.85101.99 ± 1.271.99
Freeze-thaw (3 cycles, −70 °C)LQC95.82 ± 1.95−4.1899.56 ± 1.09−0.4498.65 ± 1.08−1.35
HQC101.56 ± 1.881.5699.85 ± 1.54−0.1599.70 ± 1.93−0.30
Post preparative (5 °C for 24 h)LQC96.22 ± 1.78−3.7897.89 ± 1.35−2.11103.53 ± 1.543.53
HQC99.59 ± 1.29−0.4196.50 ± 1.99−3.50102.98 ± 1.902.98
Long-term (45 days, −70 °C)LQC96.09 ± 1.63−3.91103.05 ± 0.993.0595.69 ± 0.85−4.31
HQC102.89 ± 1.602.89101.61 ± 1.221.6196.07 ± 0.86−3.93

7 In vivo and pharmacokinetic analysis of rat plasma

The conducted HPLC method in this study was used to conduct comparative pharmacokinetic study to show the effects of co-administrating IBU versus DIC on the pharmacokinetic profile of DNT. This study is very important since usually pain killers are prescribed to relive pain associated with different musculoskeletal conditions and sometimes even misused by the patients. Thus, the effect of these drugs on DNT plasma levels must be well assessed. The proposed method is the first analytical tool to be developed for simultaneous assay of DNT with IBU/DIC and it was of sufficient accuracy and sensitivity for assessing the plasma pharmacokinetics of DNT in rats, following single oral dose. In addition, the experiment, just utilized simple protein precipitation using just acetonitrile as a precipitating agent without the need of further pH adjustments or other agents. Also, protein precipitation is known to be simple extraction procedure that does not require large amount of organic solvents and does not generate huge amount of waste. Thus, the proposed bioanalytical technique can be considered environmental friendly because of its simplicity, low cost, and low solvent consumption. After calculation of the concentrations of DNT in the plasma collected from the five rats in each group using the obtained regression equations, pharmacokinetic profiles were plotted as shown in Fig. 5. DNT plasma maximum concentration (Cmax) was 0.83 μg/mL at 5 h (Tmax) when administrated solely. In case of DIC co-administration, Cmax achieved was 0.68 μg/mL at 4 h. While in case of IBU, Cmax increased to 1.13 μg/mL at Tmax of 5 h. From Fig. 5 and those results we can conclude that, although Tmax of DNT in presence of DIC was reduced 1 h while maintaining similar Cmax compared to administrating DNT solely and Cmax of DNT in presence of IBU increased at a similar Tmax compared to DNT administration alone but all the obtained Cmax and Tmax comes in good agreement with previous report of DNT single administration without any other drugs [1] which indicates there is no significant difference on the pharmacokinetic profile of DNT upon its co-administration with the other two investigated drugs (DIC/IBU). However, further investigation is required regarding possible drug-drug interaction in case of DNT administration with DIC or IBU as it was previously reported possible hyperkalemia can take place upon co-administration [8].

Fig. 5.
Fig. 5.

Mean plasma concentration-time profiles after dosing with DNT, DNT and IBU, and DNT and DIC (n = 5).

Citation: Acta Chromatographica 2022; 10.1556/1326.2022.01089

8 Conclusion

The co-administration of muscle relaxants as DNT with NSAIDs such as IBU or DIC, for different muscular conditions, necessities the availability of an analytical tool for simultaneous analysis of these drugs together in plasma. The detailed HPLC method of this study was of enough sensitivity and accuracy to assay the two mixtures of DNT in plasma with just simple protein precipitation step. The results achieved in the analysis of DNT and IBU or DIC in rat plasma after their oral administration indicates the selectivity of the method and its validity to be used for pharmacokinetics testing of these drugs. The proposed HPLC method is considered novel as it is the first analytical tool in the literature to assay DNT in presence of two common pain killers (IBU/DIC). The co-administration effect of IBU or DIC on the pharmacokinetic curve of DNT had been carefully studied and compared with DNT pharmacokinetic profile when taken solely. Although, no significant changes was noticed in DNT “plasma concentration-time curve“ upon co-administration with IBU or DIC, further investigations are recommended to inspect any possible drug-drug interaction and can be done with the proposed analytical tool in our work. The proposed method is advantageous due to its simplicity using just simple protein precipitation for the plasma samples and commonly available chromatographic instrument without having to use mass spectroscopy to reach the required sensitivity.

Funding

Not applicable.

Conflicts of interest/competing interests

Not applicable.

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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)
  • Á. M. Móricz (Centre for Agricultural Research, 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

Indexing and Abstracting Services:

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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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