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  • 1 The People's Hospital of Lishui, Lishui 323000, China
  • | 2 Taizhou Municipal Hospital affiliated with Taizhou University, Taizhou 318000, China
  • | 3 Wenzhou Medical University, Wenzhou 325035, China
  • | 4 The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
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Eupatilin, mainly derived from Artemisia asiatica (Asteraceae), is an O-methylated flavone with various bioactivities. In the present study, a validated ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was established for the quantification of eupatilin in rat plasma with the internal standard (IS) of tussilagone and the protein precipitation of plasma samples was performed using acetonitrile–methanol (9:1, v/v). The eupatilin and IS were eluted separately on a UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) with the gradient mobile phase consisted of 0.1% formic acid and acetonitrile. The protonated analytes were quantified by multiple reactions monitoring (MRM) mode with an electrospray ionization (ESI) source operated in positive ion mode. The calibration plots were found to be linear over the range from 2 to 1000 ng/mL for eupatilin in rat plasma. Both of the intra-day and inter-day precision variations (RSDs) were ≤13%. The recoveries of eupatilin in rat plasma were between 83.7% and 94.6%, and the accuracy of the method ranged from 95.8% to 107.6%. In addition, the validated method was applied to pharmacokinetic study of eupatilin after an intravenous dose of 2 mg/kg to rats.

Abstract

Eupatilin, mainly derived from Artemisia asiatica (Asteraceae), is an O-methylated flavone with various bioactivities. In the present study, a validated ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was established for the quantification of eupatilin in rat plasma with the internal standard (IS) of tussilagone and the protein precipitation of plasma samples was performed using acetonitrile–methanol (9:1, v/v). The eupatilin and IS were eluted separately on a UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) with the gradient mobile phase consisted of 0.1% formic acid and acetonitrile. The protonated analytes were quantified by multiple reactions monitoring (MRM) mode with an electrospray ionization (ESI) source operated in positive ion mode. The calibration plots were found to be linear over the range from 2 to 1000 ng/mL for eupatilin in rat plasma. Both of the intra-day and inter-day precision variations (RSDs) were ≤13%. The recoveries of eupatilin in rat plasma were between 83.7% and 94.6%, and the accuracy of the method ranged from 95.8% to 107.6%. In addition, the validated method was applied to pharmacokinetic study of eupatilin after an intravenous dose of 2 mg/kg to rats.

Introduction

Eupatilin, a flavone derived from Artemisia plants, has been proven to possess multipharmacological activates. It is one of the antimutagens of methanol extract of gaiyou [1]. It could induce some groups of cells' apoptosis including human gastric cancer AGS cells [2] and human promyelocytic leukemia cells and induces cell cycle arrest in ras-transformed human mammary epithelial cells [3, 4]. From this point, it shows a great potential of curing cancer by inducing related cells apoptosis. Besides this, according to the research of Kang et al., eupatilin has antidiabetic activity by promoting hepatic and plasma glucose metabolism and stimulating insulin secretion in type 2 diabetic mice [5], while Choi et al. reported that eupatilin can prevent gastric mucosal injury which appeared to be affected by the increase of the gastric defensive systems [6]. From the study of Lee et al., eupatilin and jaceosidin may have the function of preventing the IgE-mediated representative skin allergic diseases, such as passive cutaneous anaphylaxis and itching reactions [7]. It shows great clinical potential in reducing hepatic, renal ischemia reperfusion injury [8, 9]. It has neuroprotective effect against ischemia/reperfusion-induced delayed neuronal damage in mice [10]. With so many great effects, it shows promising application. However, further research is still in need to confirm the relative effectiveness and achieve the pharmacokinetic characteristics of eupatilin.

Hence, the object of current study was to establish a sensitive UPLC–MS/MS method for quantitation of eupatilin in rat plasma for the first time and apply it in the investigation of the pharmacokinetic properties of eupatilin.

Experimental

Chemicals and Reagents

Eupatilin (Figure 1a) and tussilagone (IS, Figure 1b) were purchased from the Chengdu Mansite Pharmaceutical Co. Ltd. (Chengdu, China). Liquid chromatography (LC)-grade acetonitrile and methanol were obtained from Merck Company (Darmstadt, Germany). Deionized water produced by Milli-Q purification system from Millipore (Bedford, MA, USA) was used throughout the experiment. Drug-free rat blank plasma was procured from the Laboratory Animal Center of Wenzhou Medical University.

Figure 1.
Figure 1.

Chemical structure of eupatilin (A) and tussilagone (IS, B)

Citation: Acta Chromatographica Acta Chromatographica 30, 4; 10.1556/1326.2017.00320

Instrumentation and Conditions

Chromatographic separation of eupatilin and tussilagone (IS) was carried out on an ACQUITY I-Class UPLC system (Waters Corp., Milford, MA, USA) by injecting 2 μL of the sample extract onto an UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm, Waters, USA) kept at constant oven temperature of 40 °C. A gradient mobile phase with eluent A (acetonitrile) and B (water with 0.1% formic acid) was conducted for the separation at a flow rate of 0.4 mL/min. The mobile phase was in a linear gradient, where the eluent A was programmed as follows: 0–1 min, 20% to 40%; 1–2 min, 40% to 90%; 2–2.5 min, maintained at 90%; 2.5–2.6 min, 90% to 20%. Both of the eupatilin and IS were eluted separately in a total run time of 3 min.

The mass spectrometric analysis was carried out on a XEVO TQD triple quadrupole mass spectrometer, coupled with the Mass Lynx V4.1 software (Waters, Milford, MA, USA). MRM mode was used to detect the parent and daughter ion with the ESI in positive ion mode as the ionization source. To achieve the highest sensitivity for detecting eupatilin and IS, the analyte of interest was injected directly into the MS for manual tuning to optimize the MS parameters. The main experimental parameters for mass spectrum were finally set as follows: desolvation gas (nitrogen) flow, 1000 L/h; cone gas flow, 50 L/h; capillary voltage, 1.5 kV; source temperature, 150 °C; and desolvation temperature, 500 °C. Quantification was performed with transitions of m/z 345.1 → 330.1 for eupatilin and m/z 413.2 → 299.2 for IS.

Calibration Standards and Quality Control Samples

Eupatilin and tussilagone (IS) were dissolved in methanol–water (50:50, v/v), respectively, to prepare the primary stock solutions at the same concentration of 1 mg/mL. Working solutions of the IS, calibration, and controls were prepared from the stock solutions by serial dilution with methanol. All of the prepared reagents were stored at 4 °C and were warmed under room temperature (RT) before use.

Nine calibration standard plots at a level of 2, 5, 10, 20, 50, 100, 200, 500, and 1000 ng/mL were prepared by mixing 10 μL of appropriate standard working solutions with 100 μL of rat plasma, followed by 10 minute vortex mixing. Quality-control (QC) samples were prepared independently at three different concentration levels (4, 250, and 800 ng/mL), using the same method as the calibration standards. Before UPLC–MS/MS analysis, both of calibration standards and QC samples were processed by protein precipitation with acetonitrile–methanol (9:1, v/v).

Sample Preparation

Before analysis, the plasma samples were thawed to RT. Aliquots of 100 μL of the collected plasma samples were added into the previously labeled tubes and then spiked with 10 μL working solution of the IS (0.5 μg/mL). After that, 200 μL of acetonitrile–methanol (9:1, v/v) was added to precipitate protein, followed by vortex for 1.0 min. The samples were allowed to centrifuge at 12,000 g for 10 min, and clear supernatant was transferred into vials. Then, 2 μL was injected into the UPLC–MS/MS system for analysis.

Method Validation

According to the guidelines for bioanalytical method development and validation issued by the Food and Drug Administration (FDA) [11] and European Medicines Agency (EMA) [12], a series of standardized assays for precision, linearity, accuracy, selectivity, stability, and recovery was conducted [1324].

Selectivity was investigated by comparing the response at the retention times of drug-free rat plasma, a rat plasma sample, and plasma spiked with analyte at 2 ng/mL which was the lower limit of quantification (LLOQ) in present experiment.

To construct calibration curves, the determination of calibration samples was performed on three consecutive days. A calibration curve with nine points over the range of 2–1000 ng/mL was constructed by plotting the relative response to the internal standard with 1/x weighing. Correlation coefficients (r2), intercepts, and slopes were calculated by linear regression.

Matrix effect was assessed by comparing peak area responses of the spiked plasma samples at 4, 250, and 800 ng/mL (n = 6) after extraction with the ones of the standards spiked in methanol at equivalent concentrations. Matrix effect is expressed as the peak area ratio. The matrix effect of the IS was evaluated at a concentration of 50 ng/mL similarly.

The precision and accuracy of developed assay were assessed in rat plasma by determination of QC samples (4, 250, and 800 ng/mL) in six replicates. All of the intra-day and inter-day accuracy and precision over three consecutive days were tested by analyzing each QC concentration levels. The result of precision is expressed as RSD which should be within ≤15%, and the acceptance criteria for accuracy were within 85% to 115% of the actual values, except for LLOQ (≤20%) for both parameters.

Experiment to evaluate the recovery was carried out by comparing the peak area of eupatilin in pre-spiked extracted plasma samples with peak area of eupatilin in post-spiked extracted plasma samples at three QC concentration levels in six replicates. The same procedure was followed to determine the recovery of IS.

Carry-over effect was evaluated by directly injecting a blank sample just after the upper limit of quantification (ULOQ = 1000 ng/mL) samples in three replicates, after which the area response of blank sample was checked and must not exceed 20% of the LLOQ and 5% of the IS [2527].

The stability of eupatilin in rat plasma was accessed in triplicate at two concentrations levels of 4 and 800 ng/mL after the exposure to different sample storage and processing conditions. The results were compared with the freshly prepared plasma samples. Short-term stability was assessed after 2 h at RT for the spiked samples and 24 h storage under auto-sampler conditions for the ready-to-inject samples. Freeze–thaw stability was tested by analyzing QC samples after complete freeze–thaw cycles (−20 °C to RT) on three consecutive days. Long-term stability was evaluated after the storage at −20 °C for 20 days. The stability of the IS (50 ng/mL) was evaluated in similar procedure.

Pharmacokinetic Study

To study the pharmacokinetics of eupatilin, male Sprague-Dawley rats (n = 6) of average weight of 200–220 g were obtained from the Laboratory Animal Center of Wenzhou Medical University and were accommodated at the standard laboratory condition at the Laboratory Animal Center of Wenzhou Medical University. All experimental procedures and protocols were reviewed and approved by the Animal Care and Use Committee of Wenzhou Medical University and were in accordance with the Guide for the Care and Use of Laboratory Animals. Rats were left for 7 days to acclimatize, and diet was prohibited for 12 h before the experiment, but water was freely available. Blood samples (approximately 0.3 mL) were collected through the tail vein in heparinized polythene tubes at 0.0333, 0.15, 0.5, 1, 1.5, 2, 3, 4, and 6 h after a single intravenous dose of 2 mg/kg of eupatilin. The plasma was immediately separated by centrifugation at 3000 g for 10 min and stored at −20 °C until analysis.

Pharmacokinetic parameters, including Cmax, half-time (T1/2), the plasma clearance (CL), area under the plasma concentration–time curve (AUC), and apparent volume of distribution (V) were analyzed with Drug and Statistics (DAS) software (version 3.0, The People's Hospital of Lishui) by non-compartmental model.

Results

Selectivity and Matrix Effect

The typical chromatograms of a drug-free plasma sample, a blank plasma sample spiked with eupatilin and IS, and a plasma sample were shown in Figure 2. There were no quantifiable peaks observed at the retention time of the eupatilin and IS in plank samples.

Figure 2.
Figure 2.

The typical chromatograms of eupatilin and tussilagone (IS). (A) Blank plasma (eupatilin and IS free); (B) blank plasma spiked with eupatilin (2 ng/mL, LLOQ) and IS (50 ng/mL); (C) a rat plasma sample at 0.25 h after single intravenous administration of 2 mg/kg eupatilin

Citation: Acta Chromatographica Acta Chromatographica 30, 4; 10.1556/1326.2017.00320

It was observed that the matrix effect for eupatilin at three concentration levels was determined between 94.7% and 99.6% (n = 6) and the matrix effect for IS at 50 ng/mL was 97.6% (n = 6). Thus, it was considered that there were negligible effects on this method by the matrix effect from plasma.

Calibration Curve and Sensitivity

Calibration curves over three consecutive days all showed a good linear relationship throughout the concentration range of 2–1000 ng/mL which could meet the demand of eupatilin determination. The regression equation fitted is as follows: y = (4.509 × 10−3 ± 5.151 × 10−5)x + (5.556 × 10−3 ± 1.96 × 10−2) (n = 3), r2 = 0.9967, where y represents the ratios of eupatilin peak area to that of IS and x represents the plasma concentration. The y intercept of the linear equation versus 0 is statistically insignificant, P > 0.05, and analysis of linear regression of the calibration curve is shown in Figure 3. The method was validated with an LLOQ of 2 ng/mL for eupatilin. The precision and accuracy at LLOQ were 14.6% and 90.2%, respectively. The limit of detection (LOD) was defined as a signal/noise ratio of 3 and turned out to be 0.5 ng/mL for eupatilin in rat plasma.

Figure 3.
Figure 3.

Analysis of linear regression of the calibration curve. (A) Scatterplot of response (eupatilin area/IS area) versus nominal EU concentration, (B) probability graphic adjustment to normal distribution of residuals from the linear regression data, and (C) chart of standardized residuals distribution, depicting a homogeneous (nontrendy) distribution that supports the 1/x-weighting regression

Citation: Acta Chromatographica Acta Chromatographica 30, 4; 10.1556/1326.2017.00320

Precision, Accuracy, and Recovery

The intra-day and inter-day precision were ≤11% and ≤13%, respectively. The accuracy of the method was ranged from 95.8% to 107.6%. Mean recoveries of eupatilin in rat plasma were between 83.7% and 94.6%. The recovery of the IS (50 ng/mL) was 87.6%. The above results indicated that the variations were within the acceptable limit, and the developed method was suitable for precise and accurate determination of eupatilin samples.

Carry-Over

There were no significant peaks or interferences left by previous samples in blank samples on the chromatogram. What is more, 0.4 extra minutes were added to the end of the gradient elution which could wash the system between samples, thereby eliminating carry-over [25].

Stability

No significant loss of stability was observed, and the bias in concentrations of stability assay was all within ±14% of their nominal values which indicated that the analyte was stable under different processing and storage conditions.

Application

The validated method was applied in the pharmacokinetic study in rats after single intravenous administration of 2 mg/kg eupatilin. The mean plasma concentration–time profile is given in Figure 4. Preliminary pharmacokinetic parameters were determined by non-compartment analysis and are shown in Table 1.

Figure 4.
Figure 4.

Mean eupatilin plasma concentration–time profile after intravenous (2 mg/kg) administration to rats

Citation: Acta Chromatographica Acta Chromatographica 30, 4; 10.1556/1326.2017.00320

Table 1.

Pharmacokinetic parameters of eupatilin after intravenous administration (2 ng/mL) in rats (n = 6)

ParametersUnitMeanSD
iv 2 mg/kg
AUC(0 − t)ng/mL*h122.652.1
AUC(0 − ∞)ng/mL*h126.249.9
t1/2h1.51.6
CLL/h/kg18.27.4
VL/kg40.247.7
Cmaxng/mL272.8149.2

Discussion

There have been high-performance liquid chromatography (HPLC) and liquid chromatography–mass spectrometry (LC–MS) methods reported for analysis of eupatilin [28, 29]. The HPLC method was just developed for the determination of eupatilin in rat plasma, urine, bile, and liver homogenate. Ji et al. developed the LC–MS to study the metabolism of eupatilin in the rats. There, four metabolites, 3′- or 4′-O-demethyl-eupatilin glucuronide, eupatilin glucuronide, 6-O-demethyl-eupatilin, and 3′- or 4′-O-demethyl-eupatilin were identified; eupatilin glucuronide was a major metabolite in rat plasma. Both articles did not provide pharmacokinetic parameters.

Jang et al. carried out a pharmacokinetic study of eupatilin [30]. They presented some pharmacokinetic parameters of eupatilin, such as the mean terminal half-life of unchanged eupatilin was 0.101 h and the total body clearance was 121 mL/min/kg. However, they used HPLC method to determine eupatilin and no any validation of HPLC method was mentioned in their work.

In our study, we firstly developed and validated a UPLC–MS/MS method. After that, the pharmacokinetic properties of eupatilin in rats were determined. The results showed the CL of eupatilin was 18.2 ± 7.4 L/h/kg, which was higher than the result of Jang's. However, the t1/2 of eupatilin (1.5 ± 1.6 h) was longer than that of Jang's. This difference may be caused by different administration and sample collection method. Jang et al. administered eupatilin intravenously at a dose of 30 mg/kg via the femoral vein and collected the blood sample via the femoral artery which was totally different with our method. We used a simple and sensitive UPLC–MS/MS to determine the concentration of eupatilin, while Jang et al. selected HPLC. Whether it was the UPLC–MS/MS or HPLC method used, the pharmacokinetic results showed that eupatilin was eliminated fast in rats. Our studies will help to build a better understanding of the pharmacological features of eupatilin.

Conclusion

In the present study, a simple, precise, and accurate UPLC–MS/MS method for the quantitation of eupatilin in rat plasma was established, utilizing 100 μL of plasma with an LLOQ of 2 ng/mL. The method is validated in terms of specificity, linearity, precision, accuracy, stability, extraction recovery, and matrix effect and has been confirmed to be well fitted for the determination of eupatilin. The validated method was applied to a pharmacokinetic study of eupatilin after an intravenous dose of 2 mg/kg to rats. The results revealed part of the in vivo process of eupatilin, which can be a reference in further research.

Acknowledgments

This study was supported by grants from the Youth Talent Program Foundation of The First Affiliated Hospital of Wenzhou Medical University (no. qnyc043).

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  • 1.

    Nakasugi T. ; Nakashima M.; Komai K. J. Agric. Food Chem. 2000, 48, 32563266.

  • 2.

    Kim M. J. ; Kim D. H.; Na H. K.; Oh T. Y.; Shin C. Y.; Surh Ph D. P. Y. J. J Environ. Pathol. Toxicol. Oncol. 2005, 24, 261269.

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

    Kim D. H. ; Na H. K.; Oh T. Y.; Kim W. B.; Surh Y. J. Biochem. Pharmacol. 2004 68, 10811087.

  • 4.

    Seo H. J. ; Surh Y. J. Mutat. Res. 2001, 496, 191198.

  • 5.

    Kang Y. J. ; Jung U. J.; Lee M. K.; Kim H. J.; Jeon S. M.; Park Y. B.; Chung H. G.; Baek N. I.; Lee K. T.; Jeong T. S.; Choi M. S. Diabetes Res. Clin. Pract. 2008, 82, 2532.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Choi S. M. ; Shin J. H.; Kang K. K.; Ahn B. O.; Yoo M. Dig. Dis. Sci. 2007 52, 30753080.

  • 7.

    Lee S. H. ; Bae E. A.; Park E. K.; Shin Y. W.; Baek N. I.; Han E. J.; Chung H. G.; Kim D. H. Int. Immunopharmacol. 2007, 7 16781684.

  • 8.

    Lee H. M. ; Jang H. J.; Kim S. S.; Kim H. J.; Lee S. Y.; Oh M. Y.; Kwan H. C.; Jang D. S.; Eom D. W. Transplant. Proc. 2016, 48, 12261233.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Jeong E. K. ; Jang H. J.; Kim S. S.; Oh M. Y.; Lee D. H.; Eom D. W.; Kang K. S.; Kwan H. C.; Ham J. Y.; Park C. S.; Jang D. S.; Han D. J. Transplant. Proc. 2015, 47, 757762.

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

    Cai M. ; Phan P. T.; Hong J. G.; Kim D. H.; Kim J. M.; Park S. J.; Liu X.; Han J. E.; Park H.; Choi J. W.; Ryu J. H. Eur. J. Pharmacol. 2012, 689, 104110.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    U.S. Department of Health and Human Services Food and Drug Administration Draft https://www.fda.gov/downloads/Drugs/Guidances/ucm368107.pdf, September 2013.

    • Search Google Scholar
    • Export Citation
  • 12.

    EMEA/CHMP/EWP/192217/2009 Committee for Medicinal Products for Human Use (CHMP) http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/08/WC500109686.pdf, July 2011.

    • Search Google Scholar
    • Export Citation
  • 13.

    Wang S. ; Wu H.; Geng P.; Lin Y.; Liu Z.; Zhang L.; Ma J.; Zhou Y.; Wang X.; Wen C. Biomed. Chromatogr. 2016, 30 11451149.

  • 14.

    Wen C. ; Wang S.; Huang X.; Liu Z.; Lin Y.; Yang S.; Ma J.; Zhou Y.; Wang X. Biomed. Chromatogr. 2015, 29 18051810.

  • 15.

    Wang X. ; Wang S.; Ma J.; Ye T.; Lu M.; Fan M.; Deng M.; Hu L.; Gao Z. J. Pharm. Biomed. Anal. 2015, 115, 368374.

  • 16.

    Ma J. S. ; Wang S. H.; Huang X. L.; Geng P. W.; Wen C. C.; Zhou Y. F.; Yu L. S.; Wang X. Q. J. Pharm. Biomed. Anal. 2015, 111, 131137.

  • 17.

    Wen C. ; Zhang Q.; He Y.; Deng M.; Wang X.; Ma J. Acta. Chromatogr. 2015, 1, 111.

  • 18.

    Wen C. C. ; Lin C. L.; Cai X. J.; Ma J. S.; Wang X. Q. J. Chromatogr. B. 2014, 944, 3538

  • 19.

    Wang S. H. ; Wu H. Y.; Huang X. L.; Geng P. W.; Wen C. C.; Ma J. S.; Zhou Y. F.; Wang X. Q. J. Chromatogr. B. 2015, 990, 118124.

  • 20.

    Zhang Q. W. ; Wen C. C.; Xiang Z.; Ma J. S.; Wang X. Q. J. Pharm. Biomed. Anal. 2014, 90, 134138.

  • 21.

    Wen C. C. ; Wang S. H.; Huang X. L.; Liu Z. Z.; Lin Y. Y.; Yang S. P.; Ma J. S.; Zhou Y. F.; Wang X. Q. Biomed. Chromatogr. 2015, 29, 18051810.

  • 22.

    Wang X. ; Wang S.; Lin F.; Zhang Q.; Chen H.; Wang X.; Wen C.; Ma J.; Hu L. J. Chromatogr. B. 2015, 983–984, 125131.

  • 23.

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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%
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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)

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