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Aiguo Zhang Department of Geriatrics, Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, China

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Hanqi Zhang Analytical and Testing Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China

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Xianqin Wang Analytical and Testing Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China

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Shuangqian Chen Department of Rehabilitation Therapy, Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, China

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Yongxi Jin Department of Rehabilitation, Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, China

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Open access

Abstract

In this study, a UPLC-MS/MS method was developed for determination of pancratistatin in the mouse blood, and the pharmacokinetics of pancratistatin in mice after intravenous (5 mg kg−1) and intragastric (15 mg kg−1) administration was studied. HSS T3 column was used for separation with mobile phases of acetonitrile and 0.1% formic acid using gradient elution procedure. The blood sample was treated by protein precipitant with acetonitrile, midazolam was used as internal standard (IS). Multiple reaction monitoring mode (MRM) was used for quantitative analysis, m/z 326.2→83.8 for pancratistatin and m/z 326.2→291.4 for IS in electrospray (ESI) positive interface. It showed a good linear in the range of 10–4,000 ng mL−1 (r > 0.998); the intra-day and inter-day precision was <15%, and the accuracy was 93%–105%. The recovery was better than 82%, and the matrix effect was 94%–105%. The developed UPLC-MS/MS method was fast, selective, and suitable for the pharmacokinetics of pancratistatin in mice.

Abstract

In this study, a UPLC-MS/MS method was developed for determination of pancratistatin in the mouse blood, and the pharmacokinetics of pancratistatin in mice after intravenous (5 mg kg−1) and intragastric (15 mg kg−1) administration was studied. HSS T3 column was used for separation with mobile phases of acetonitrile and 0.1% formic acid using gradient elution procedure. The blood sample was treated by protein precipitant with acetonitrile, midazolam was used as internal standard (IS). Multiple reaction monitoring mode (MRM) was used for quantitative analysis, m/z 326.2→83.8 for pancratistatin and m/z 326.2→291.4 for IS in electrospray (ESI) positive interface. It showed a good linear in the range of 10–4,000 ng mL−1 (r > 0.998); the intra-day and inter-day precision was <15%, and the accuracy was 93%–105%. The recovery was better than 82%, and the matrix effect was 94%–105%. The developed UPLC-MS/MS method was fast, selective, and suitable for the pharmacokinetics of pancratistatin in mice.

Introduction

Hymenocallis littoralis is a perennial herb of the genus Hymenocallis of Amaryllidaceae, also known as spider orchid [1, 2]. Its main components are alkaloids, including pancratistatin, narciclasine, 7-deoxynarciclasine, tazettine, lycorine, homolycorine, etc., [3]. Among them, pancratistatin, narciclasine, 7-deoxynarciclasine have been found to have effective anti-tumor effects [4–7]. As one of the main anti-tumor active components of the alkaloids from the H. littoralis, pancratistatin was first found to have cytotoxic effects on human cancer cell lines in 1993 [8]. Pancratistatin can inhibit the growth of tumor cells, induce apoptosis of tumor cells, and inhibit the synthesis of DNA, RNA and protein in tumor cells [9]. It has been shown that the main anticancer activity center of pancratistatin is isoquinolone ring skeleton structure.

At present, pancratistatin has been proved to selectively induce apoptosis of a variety of human cancer cells, but has no significant effect on non-cancer cells [10]. Natasha Kekre studied human lymphoma cells (Jurkat), and found that pancratistatin in Jurkat cells caused early activation of caspase-3 and reversal of phosphatidylserine, and induced cancer cells to use non genomic target cells to apoptosis [11]. Compared with the commonly used etoposide (VP-16), pancratistatin shows stronger specificity and will not cause any DNA damage in non-cancer cells [11]. McLachlan et al. conducted an experimental study on the effect of pancratistatin on human neuroblastoma (SHSY-5Y cells), and found that pancratistatin had an obvious inhibitory effect on the proliferation of SHSY-5Y cells [12]. It is suggested that pancratistatin may induce SHSY-5Y cell apoptosis through mitochondrial pathway. Griffin reported the effect of pancratistatin on metastatic prostate cancer model, and evaluated the effect of pancratistatin on prostate cancer cell lines DU145 and LNCaP [13]. Treatment with pancratistatin reduced the cell viability of androgen response (LNCaP) and androgen refractory (DU145) prostate cancer cell lines, and induced apoptosis in a dose time dependent manner, it has no significant effect on normal human fibroblasts (NHF) [14]. In these two cancer cell lines, the treatment with pancratistatin can increase the production of reactive oxygen species and the collapse of mitochondrial membrane potential, and it was found that pancratistatin treatment can reduce the migration ability of metastatic prostate cancer cells and increase the autophagy level [15].

However, the study on the pharmacokinetics of pancratistatin in vivo has not been reported. Therefore, it is necessary to clarify the pharmacokinetics in vivo. In this work, a rapid and selective UPLC-MS/MS method for the determination of pancratistatin in mouse blood was established for the pharmacokinetic in vivo.

Experimental

Chemicals and reagents

Pancratistatin (purity ≥98%, Fig. 1a) was obtained from Chengdu Manster Pharmaceutical Co., Ltd (Chengdu, China). Midazolam (internal standard (IS), purity ≥98%, Fig. 1b) was obtained from Merck (Darmstadt, Germany). HPLC pure methanol and acetonitrile were obtained from Merck Co., Ltd. (Darmstadt, Germany). Ultra-pure water was obtained by Millipore Milli-Q purification system (Bedford, Ma, USA).

Fig. 1.
Fig. 1.

Chemical structure of pancratistatin (a) and internal standard (midazolam, b)

Citation: Acta Chromatographica 36, 2; 10.1556/1326.2023.01114

UPLC-MS/MS method

Acquity H-class UPLC and Xevo TQS micro triple quadrupole mass spectrometer with electrospray ionization (ESI) (Waters Corp, Milford, MA, USA) was used in this work.

UPLC HSS T3 column (2.1 mm × 50 mm, 1.7 μm) (Waters Corp, Milford, MA, USA) was used for separation. The mobile phase was composed of acetonitrile and 0.1% formic acid. The gradient elution procedure was: 0–0.2 min, acetonitrile 10%; 0.2–1.0 min, acetonitrile 10%–70%; 1.0–2.5 min, acetonitrile 70%–90%; 2.5–2.8 min, acetonitrile 90%–10%; 2.8–4.0 min, acetonitrile 10%. The column temperature was set at 40 °C. The injection volume was 2 μL. The flow rate was set at 0.4 mL min−1.

Nitrogen was used as desolvation gas (900 L h−1) and cone gas (50 L h−1). The capillary voltage was set at 2.4 kV, the ion source temperature was 150 °C and the desolvation temperature was 400 °C. MRM was used for quantitative analysis, pancratistatin m/z 326.2→83.8 (cone voltage 30 V, collision voltage 20 V) and internal standard ion m/z 326.2→291.4 (cone voltage 25 V, collision voltage 25 V), in ESI positive ion mode, Fig. 2.

Fig. 2.
Fig. 2.

Mass spectrum of pancratistatin (a) and internal standard (midazolam, b)

Citation: Acta Chromatographica 36, 2; 10.1556/1326.2023.01114

Preparation of standard series samples and quality control samples

The reference substance of pancratistatin was accurately weighed, and dissolved with methanol-water (50:50, v/v) to obtain a stock solution of pancratistatin with a concentration of 1.0 mg mL−1, which was used to prepare standard working solutions and quality control (QC) working solutions respectively.

The stock solution and QC stock solution of pancratistatin were diluted with methanol-water (50:50, v/v) to obtain standard working solutions with concentrations of 100, 200, 400, 1,000, 2,000, 4,000, 10,000, 20,000, 40,000 ng mL−1 and QC working solutions with concentrations of 100, 180, 3,600, 36,000 ng mL−1. A portion of midazolam reference substance was accurately weighed, and dissolved in methanol-water (50:50, v/v) to obtain an IS stock solution with a concentration of 1.0 mg mL−1. Then it was diluted with methanol-water (50:50, v/v) to obtain an IS working solution of midazolam with a concentration of 500 ng mL−1.

Appropriate standard working solution and QC working solution were added into blank blood, and a concentration of 10, 20, 40, 100, 200, 400, 1,000, 2,000, 4,000 ng mL−1 and the QC samples with a concentration of 10, 18, 360, 3,600 ng mL−1 were obtained.

Blood sample pretreatment

Took blood sample 20 μL, and added 10 μL IS solution (midazolam, concentration 500 ng mL−1), then added acetonitrile 100 μL. Vortex for 1 min and centrifuged at 13,000 rpm for 10 min. Took the supernatant 2 μL for UPLC-MS/MS analysis.

Method validation

The selectivity, standard curve and lower limit of quantification (LLOQ), precision and accuracy, stability, recovery and matrix effect of the method were verified “[16].

Selectivity

Blank mouse blood, blank blood spiked with pancratistatin and IS, and a mouse blood sample were analyzed by UPLC-MS/MS to see if there was interference in the determination.

Standard curve

The sample treatment was conducted according to the item of “Blood sample pretreatment”. With the concentration of each substance to be measured as the abscissa and the peak area ratio of the substance to be measured and the IS as the ordinate, the weighted (W = 1/x2) least square method was used for regression calculation. The correlation coefficients (r2) of the standard curves obtained were all greater than 0.99.

Lower limit of quantification

The LLOQ was defined as the lowest concentration on the calibration curves, with the signal-to-noise ratio better than 5. Took LLOQ blood samples, analyze 6 samples, measure for 3 consecutive days, calculated the measured concentration of each sample according to the standard curve of the day, and the intra-day and inter-day precision and accuracy of the concentration were determinated.

Precision and accuracy

Take QC samples of pancratistatin, and operate according to the item of “Blood sample pretreatment”. Analyze 6 samples of each concentration, and determine the intra-day and inter-day precision and accuracy within 3 days.

Matrix effect

Took 20 μL blank blood from six different sources, and added acetonitrile 100 μL, vortex for 1 min and centrifuge for 10 min. Took the supernatant 90 μL, added 10 μL of the control solution of pancratistatin and IS working solution 10 μL. Vortex mixing, took 2 μL to perform UPLC-MS/MS analysis to obtain the peak areas of the corresponding analyte and IS respectively. Meanwhile, another 20 μL water replaces the blank blood, and the peak areas of the corresponding analyte and IS were obtained. Calculated the matrix effect of analyte and IS respectively by the peak area ratio of the two treatment methods.

Recovery

The QC sample were prepared with mouse blank blood. The operation was performed under the item of “Blood sample pretreatment”. Six samples were analyzed for each concentration (A). Meanwhile, took another 20 μL blank blood, added acetonitrile 100 μL. Vortex for 1 min and centrifuged for 10 min. Took the supernatant 90 μL, added 10 μL of the control solution of pancratistatin and 10 μL IS working solution. Vortex mixing, six samples for each concentration (B). Took 2 μL to perform UPLC-MS/MS analysis. Calculated the recovery by the peak area ratio of two treatment methods for each concentration, and the calculation formula was A/B × 100%.

Stability

To investigate the stability of blood sample of pancratistatin at room temperature for 24 h, after being treated with precipitated protein for 24 h, after undergoing three freezing thawing cycles at –20 °C, and after long-term storage at –20 °C [17, 18].

Pharmacokinetics

Institute of cancer research (ICR) mice (weight 20–22 g) were obtained from the animal experiment center of Wenzhou Medical University (Wenzhou, China). Twelve mice were randomly divided into two groups, one group was given gavage (15 mg kg−1) and another group was given intravenously (5 mg kg−1), with six mice in each group. All experimental procedures and protocols were approved by the Animal Care Committee of Wenzhou Medical University. Twenty microliter blood samples were taken from the tail vein of mice in 1.5 mL heparinized Eppendorf tubes at 0.0833, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h after administration of pancratistatin, frozen at –20 °C. Pharmacokinetic parameters were calculated by Das 2.0 software (Shanghai University of traditional Chinese Medicine) [19], such as area under the concentration-time curve (AUC), the half-life (t1/2), clearance (CL), mean resident time (MRT), volume of distribution (V), and peak blood concentrations (Cmax). Absolute bioavailability (%) = 100 × AUCig × Div/(AUCiv × Dig), where AUCiv and AUCig were the AUC of the drug after intravenous and intragastric administration and Div and Dig were a single dosage of pancratistatin for intravenous and intragastric administration, respectively [20, 21].

Results and discussion

Chromatographic condition selection

Different brands and specifications of chromatographic columns was tried, such as Waters BEH C18 (50 mm × 2. 1 mm, 1.7 μ m), Waters HSS T3 (50 mm × 2. 1 mm, 1.7 μm), Waters CORTECS T3 (50 mm × 2.1 mm, 1.7 μm), and Agilent ZORBAXSB-C18 (50 mm × 2.1 mm, 1.8 μ m). The results showed that Waters HSS T3 (50 mm × 2.1 mm, 1.7 μm), the chromatographic column had better separation effect and the retention time of the analyte and IS was appropriate. The separation of methanol-water and water-acetonitrile as mobile phases was compared. The results showed that the acetonitrile-water system had relatively good peak shape. It was found that the addition of 0.1% formic acid aqueous solution could significantly improve the peak shape of the analyte and increase the mass spectrum response.

Selection of plasma sample pretreatment method

The extraction effects of protein precipitation method (PPT) and liquid-liquid extraction (LLE) were compared. It was found that the extraction recovery obtained by LLE method was lower, while the PPT method could not only eliminate the interference of matrix, but also have higher recovery and more convenient operation. At the same time, the extraction effects of methanol, acetonitrile and methanol acetonitrile (volume ratio 1:1) as precipitants were compared. The results showed that the highest recovery was obtained when acetonitrile was used as precipitant.

Selection of internal standard

In the analysis of biological samples, the ideal IS having good solubility, no chemical reaction with the measured sample, and its peak position should be close to the analyte peak. In this study, midazolam, diazepam, carbamazepine and tolbutamide were tried as IS successively. And midazolam met the necessary conditions for being the IS, which had a similar behavior of chromatographic retention time and the ionization mass spectrometry to pancratistatin.

Selectivity

Figure 3 shows that the retention time of pancratistatin and IS was 1.43 and 1.72 min, respectively. No obvious endogenous substances interfere with the detection.

Fig. 3.
Fig. 3.

UPLC-MS/MS of pancratistatin and internal standard in mouse blood, (a) blank mouse blood, (b) blank mouse blood spiked with pancratistatin (LLOQ) and internal standard (midazolam), (c) a mouse blood after intragastric (ig, 15 mg kg−1) administration

Citation: Acta Chromatographica 36, 2; 10.1556/1326.2023.01114

Linearity

The standard curve equation of pancratistatin in the range of 10–4,000 ng mL−1 in mouse blood was y = 0.000033x–0.000045, r = 0.9981. Where y represents the peak area ratio of pancratistatin to IS, and x represents the concentration of pancratistatin in blood. The LLOQ of pancratistatin in mouse blood was 10 ng mL−1, with the signal-to-noise ratio of 10.

Precision, accuracy, recovery, and matrix effect

The intra-day precision of pancratistatin in mouse blood is less than 14%, the intra-day precision is less than 15%, the accuracy is 93%–105%. The recovery is better than 82%, and the matrix effect is 94%–105% (Table 1).

Table 1.

Accuracy, precision, matrix effect and recovery of pancratistatin in mouse blood

Concentration (ng mL−1)Precision (RSD%)Accuracy (%)Matrix effect (%)Recovery (%)
Intra-dayInter-dayIntra-dayInter-day
1013.813.493.794.2100.282.2
189.214.593.0104.2104.796.0
3607.511.299.693.3100.088.7
3,6006.98.9103.195.494.187.8

Stability

The variation of pancratistatin in the blood of mice was within ±13% and RSD was within 15%, indicating that pancratistatin was stable, Table 2.

Table 2.

Stability of pancratistatin in mouse blood

Concentration (ng mL−1)Autosampler (4 °C, 12 h)Ambient (2 h)−20 °C (30 d)Freeze-thaw
AccuracyRSDAccuracyRSDAccuracyRSDAccuracyRSD
1898.69.294.914.0104.114.2112.414.0
360106.16.796.011.388.010.492.612.5
3,600101.46.6102.09.095.911.488.413.8

Pharmacokinetics

The main pharmacokinetic parameters were fit by non-compartmental model, as showed in Table 3. The blood concentration time curve was shown in Fig. 4. The bioavailability of pancratistatin in mice (15 mg kg−1) was 2.9%. The pharmacokinetics of narciclasine in mice was studied in our previous work [22], pancratistatin is the close structural analogue of narciclasine, however, t1/2 of narciclasine was 1.7 ± 0.2 h, AUC(0–t) was 2448.1 ± 408.6 ng mL−1*h, was different from pancratistatin.

Table 3.

Main pharmacokinetic parameters after intravenous (iv, 5 mg kg−1) and intragastric (ig, 15 mg kg−1) administration of pancratistatin in mice

ParametersUnitIG (15 mg kg−1)IV (5 mg kg−1)
AUC(0–t)ng × h mL−1506.8 ± 56.95757.3 ± 479.0
AUC(0–∞)ng × h mL−1518.2 ± 62.27282.8 ± 2650.1
MRT(0–t)h3.1 ± 0.23.8 ± 0.3
MRT(0–∞)h3.4 ± 0.35.3 ± 1.7
t1/2zh2.2 ± 0.75.2 ± 4.7
Tmaxh2.0-
CLz/FL h−1 kg−129.3 ± 3.70.7 ± 0.2
Vz/FL kg−193.5 ± 22.54.5 ± 2.1
Cmaxng mL−1201.8 ± 56.11452.7 ± 216.2
Absolute bioavailability2.9%
Fig. 4.
Fig. 4.

The concentration-time curve of mice after intravenous (iv, 5 mg kg−1) and intragastric (ig, 15 mg kg−1) administration of pancratistatin in mice

Citation: Acta Chromatographica 36, 2; 10.1556/1326.2023.01114

Conclusion

In this work, we established a rapid, exclusive and accurate LC-MS/MS method for the determination of pancratistatin concentration in mouse blood, and successfully applied the method to the pharmacokinetic study of pancratistatin in mice, while providing a scientific basis for the clinical application of pancratistatin.

Conflict of interest statement

The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Acknowledgements

This work was supported by Wenzhou science and Technology Bureau (Y2020882).

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    Zhang, J.; Sayakoummane, S.; Kim, S. A.; Lee, J. S.; Choung, E. S.; Kim, E. S.; Lee, S. G.; Yum, J.; Lee, B. H.; Lee, S.; Kim, J. H.; Cho, J. Y. J. Ethnopharmacol 2022, 295, 115400.

    • Search Google Scholar
    • Export Citation
  • 2.

    Ma, W.; Wang, S.; Wang, Y.; Zeng, J.; Xu, J.; He, X. Phytochemistry 2022, 197, 113112.

  • 3.

    Yousef, B. A.; Dirar, A. I.; Elbadawi, M. A. A.; Awadalla, M. K.; Mohamed, M. A. J. Pharm. Bioallied Sci. 2018, 10, 137143.

  • 4.

    Abou-Donia, A. H.; Toaima, S. M.; Hammoda, H. M.; Shawky, E.; Kinoshita, E.; Takayama, H. Chem. Biodivers 2008, 5, 332340.

  • 5.

    Lin, L. Z.; Hu, S. F.; Chai, H. B.; Pengsuparp, T.; Pezzuto, J. M.; Cordell, G. A.; Ruangrungsi, N. Phytochemistry 1995, 40, 12951298.

    • Search Google Scholar
    • Export Citation
  • 6.

    Habartova, K.; Cahlikova, L.; Rezacova, M.; Havelek, R. Nat. Prod. Commun. 2016, 11, 15871594.

  • 7.

    Kornienko, A.; Evidente, A. Chem. Rev. 2008, 108, 19822014.

  • 8.

    Pettit, G. R.; Pettit, G. R. 3rd; Backhaus, R. A.; Boyd, M. R.; Meerow, A. W. J. Nat. Prod. 1993, 56, 16821687.

  • 9.

    McNulty, J.; Mao, J.; Gibe, R.; Mo, R.; Wolf, S.; Pettit, G. R.; Herald, D. L.; Boyd, M. R. Bioorg. Med. Chem. Lett. 2001, 11, 169172.

    • Search Google Scholar
    • Export Citation
  • 10.

    Castillo, S. R.; Rickeard, B. W.; DiPasquale, M.; Nguyen, M. H. L.; Lewis-Laurent, A.; Doktorova, M.; Kav, B.; Miettinen, M. S.; Nagao, M.; Kelley, E. G.; Marquardt, D. Mol. Pharm. 2022, 19, 18391852.

    • Search Google Scholar
    • Export Citation
  • 11.

    Kekre, N.; Griffin, C.; McNulty, J.; Pandey, S. Cancer Chemother. Pharmacol. 2005, 56, 2938.

  • 12.

    McLachlan, A.; Kekre, N.; McNulty, J.; Pandey, S. Apoptosis 2005, 10, 619630.

  • 13.

    Griffin, C.; Hamm, C.; McNulty, J.; Pandey, S. Cancer Cell Int. 2010, 10, 6.

  • 14.

    Griffin, C.; Karnik, A.; McNulty, J.; Pandey, S. Mol. Cancer Ther. 2011, 10, 5768.

  • 15.

    Griffin, C.; McNulty, J.; Pandey, S. Int. J. Oncol. 2011, 38, 15491556.

  • 17.

    Xu, Y.; Chen, X.; Zhong, D. Biomed. Chromatogr. 2019, 33, e4422.

  • 18.

    Wang, L.; Shen, H.; Zhan, Y.; Zhang, Y.; Zhang, Y.; Chen, M.; Li, X.; Zhong, D. J. Pharm. Biomed. Anal 2023, 225, 115203.

  • 19.

    Huang, X.; Jiang, H.; Liang, Q.; Ma, Y.; Wang, X. Biomed. Chromatogr. 2022, 36, e5419.

  • 20.

    Li, T.; Ye, W.; Huang, B.; Lu, X.; Chen, X.; Lin, Y.; Wen, C.; Wang, X. J. Pharm. Biomed. Anal 2019, 168, 133137.

  • 21.

    Chen L., Zhang, B., Liu, J., Fan, Z., Weng, Z., Geng, P., Wang, X.; Lin, G. Biomed. Res. Int. 2018: 1578643.

  • 22.

    Ren, K.; Feng, T. T.; Shi, H.; Ma, J. S.; Jin, Y. X. Acta Chromatographica 2022, 34, 115119.

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Senior editors

Editor(s)-in-Chief: Kowalska, Teresa (1946-2023)

Editor(s)-in-Chief: Sajewicz, Mieczyslaw, University of Silesia, Katowice, Poland

Editors(s)

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

Editorial Board

  • Ravi Bhushan, The Indian Institute of Technology, Roorkee, India
  • Jacek Bojarski, Jagiellonian University, Kraków, Poland
  • Bezhan Chankvetadze, State University of Tbilisi, Tbilisi, Georgia
  • Michał Daszykowski, University of Silesia, Katowice, Poland
  • Tadeusz H. Dzido, Medical University of Lublin, Lublin, Poland
  • Attila Felinger, University of Pécs, Pécs, Hungary
  • Kazimierz Glowniak, Medical University of Lublin, Lublin, Poland
  • Bronisław Glód, Siedlce University of Natural Sciences and Humanities, Siedlce, Poland
  • Anna Gumieniczek, Medical University of Lublin, Lublin, Poland
  • Urszula Hubicka, Jagiellonian University, Kraków, Poland
  • Krzysztof Kaczmarski, Rzeszow University of Technology, Rzeszów, Poland
  • Huba Kalász, Semmelweis University, Budapest, Hungary
  • Katarina Karljiković Rajić, University of Belgrade, Belgrade, Serbia
  • Imre Klebovich, Semmelweis University, Budapest, Hungary
  • Angelika Koch, Private Pharmacy, Hamburg, Germany
  • Piotr Kus, Univerity of Silesia, Katowice, Poland
  • Debby Mangelings, Free University of Brussels, Brussels, Belgium
  • Emil Mincsovics, Corvinus University of Budapest, Budapest, Hungary
  • Ágnes M. Móricz, Centre for Agricultural Research, Budapest, Hungary
  • Gertrud Morlock, Giessen University, Giessen, Germany
  • Anna Petruczynik, Medical University of Lublin, Lublin, Poland
  • Robert Skibiński, Medical University of Lublin, Lublin, Poland
  • Bernd Spangenberg, Offenburg University of Applied Sciences, Germany
  • Tomasz Tuzimski, Medical University of Lublin, Lublin, Poland
  • Yvan Vander Heyden, Free University of Brussels, Brussels, Belgium
  • Adam Voelkel, Poznań University of Technology, Poznań, Poland
  • Brata Walczak, University of Silesia, Katowice, Poland
  • Wiesław Wasiak, Adam Mickiewicz University, Poznań, Poland
  • Igor G. Zenkevich, St. Petersburg State University, St. Petersburg, Russian Federation

 

KOWALSKA, TERESA (1946-2023)
E-mail: kowalska@us.edu.pl

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

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2023  
Web of Science  
Journal Impact Factor 1.7
Rank by Impact Factor Q3 (Chemistry, Analytical)
Journal Citation Indicator 0.43
Scopus  
CiteScore 4.0
CiteScore rank Q2 (General Chemistry)
SNIP 0.706
Scimago  
SJR index 0.344
SJR Q rank Q3

Acta Chromatographica
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Gold Open Access
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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
1988
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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