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  • 1 Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland
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In this study, the in vitro phase I metabolism of lacosamide was characterized with the use of ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry (quadrupole time-of-flight). The use of two metabolism simulation techniques (photocatalysis and human liver microsomes) allowed the characterization of a polar metabolite of parent compound, not yet described. The experiment with the participation of HLM gave the ability to describe the full liver metabolic pathway of lacosamide. It has been proven that this molecule undergoes deacetylation, demethylation, and during liver tissue metabolism. Photocatalysis with the use of a TiO2 catalyst was proved to be a complementary technique in mimicking in vitro drug metabolism.

Abstract

In this study, the in vitro phase I metabolism of lacosamide was characterized with the use of ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry (quadrupole time-of-flight). The use of two metabolism simulation techniques (photocatalysis and human liver microsomes) allowed the characterization of a polar metabolite of parent compound, not yet described. The experiment with the participation of HLM gave the ability to describe the full liver metabolic pathway of lacosamide. It has been proven that this molecule undergoes deacetylation, demethylation, and during liver tissue metabolism. Photocatalysis with the use of a TiO2 catalyst was proved to be a complementary technique in mimicking in vitro drug metabolism.

Introduction

Drugs, as molecules of non-natural chemical character for the human, are subjected to processes of absorption, distribution, metabolism, and excretion (known as ADME), regardless of the route of their administration [13]. Metabolism is one of the most important elements of this sequence. Its detailed knowledge provides a lot of valuable information, which may allow, for instance, the improvement of the absorption of the molecule at the site of administration. It is estimated that almost 10% of marketed drugs are distributed in the prodrug form, which are chemically converted into an active form after dosage. Prodrugs are usually less active or inactive, but their specific physicochemical properties help to improve the bioavailability of compounds [46]. On the other hand, undesirable toxic products may also appear in the phase I of metabolism of the therapeutic substance. Therefore, understanding the exact metabolism of drugs has a huge impact on the production of new drugs. It is an expensive process, and the occurrence of unforeseeable toxic or reactive products of biotransformation is definitely not recommended.

The liver is an organ responsible for the metabolism of many drugs [7, 8]. In order to minimize the costs and accelerate the research procedure, human liver microsomes (HLMs) were successfully used to simulate these processes. During the incubation of an analyzed drug with HLMs, it is possible to obtain information about metabolic pathways and to achieve biotransformation products that can be subjected to more detailed investigation.

A further attempt to reduce costs and human inputs, with simultaneous simplification of the procedure, resulted in the development of a method for simulating metabolism with the use of photocatalysis. Irradiation of a drug substance solution in the presence of photocatalyst molecules (TiO2) with a specific wavelength causes the oxidation in a manner similar to the processes of biotransformation [9]. The use of the combination of both biological and photocatalytic techniques can be considered as a complementary tool in drug metabolism investigations [1014].

Epilepsy is the one of the most common human neurological disorders, and it is connected with brain dysfunction, which reveals recurrent epileptic seizures caused by the abnormal activity of brain neurons. The disease has important, negative neurobiological, psychological, and cognitive consequences [15, 16]. The difficulty of the treatment with still high mortality has become the reason for searching for new and convenient pharmacological therapies [17].

Lacosamide, (R)-2-acetamido-N-benzyl-3-methoxypropionamide, is an anti-epileptic drug (AED) mainly used as a support in therapy of focal onset seizures, as well as neuropathic pain disease [18]. In 2017, European Medicines Agency allowed its application in the partial-onset seizures treatment of patients aged 4 years and older [19, 20]. Lacosamide stands out from other AEDs due to the novel mechanism of its action. Drug molecule selectively enhances slow inactivation of voltage-gated sodium channels. Unlike others, it does not affect the fast inactivation route. This action results in the stabilization of hyperexcitable neuronal membranes, which prevents seizures [2124]. Lacosamide undergoes hepatic metabolism, mainly through the CYP2C19 enzymes; however, the exact biotransformation pathway has not been described yet. It was found that the main metabolite is O-desmethyl lacosamide with no anticonvulsant activity. Other metabolites, especially from polar fraction, have not been characterized so far [25, 26].

The main goal of this study was to characterize the lacosamide phase I metabolites in human liver microsomes and to compare the obtained results with photocatalysis transformation processes based on the use of TiO2. The use of both techniques allowed the establishment of complete hepatic metabolism pathway of lacosamide. Moreover, a polar metabolite of lacosamide, which is not so far described, was structurally characterized.

Materials and Methods

Chemicals and Reagents

Pharmaceutical formulation of lacosamide (Vimpat) was obtained in a local pharmacy, and water (LC–MS Ultra grade), β-nicotinamide adenine dinucleotide 2′-phosphate (NADPH)-reduced tetrasodium salt hydrate, human liver microsomes, sodium phosphate monobasic monohydrate salt, sodium phosphate dibasic anhydrous salt, tungsten (VI) oxide nanopowder 100 nm particle size, and titanium (IV) oxide nanopowder 21 nm particle size (Aeroxide® 25) were obtained from Sigma-Aldrich (St. Louis, USA). Acetonitrile (hypergrade for LC–MS) was purchased from Merck (Darmstadt, Germany), and 98% formic acid (LC–MS grade) was obtained from Fluka (Taufkirchen, Germany).

Ultra-High-Performance Liquid Chromatography–Electrospray Ionization–High-Resolution Mass Spectrometry (UHPLC–ESI–HRMS) Analysis

LC–MS analysis was performed with the use of a high-resolution (HR) Agilent Accurate-Mass Quadrupole Time-of-Flight (Q-TOF) LC/MS G6520B system with a dual electrospray ionization (DESI) source and an Infinity 1290 ultra-high pressure liquid chromatography system consisting of a binary pump G4220A, a FC/ALS thermostat G1330B, autosampler G4226A, a diode-array detector (DAD) G4212A, a thermostatted column compartment (TCC) G1316C module (Agilent Technologies, Santa Clara, USA), and a Kinetex C18 (2.1 mm × 50 mm, dp = 1.7 μm) column with a C18 precolumn guard (Phenomenex, Torrance, USA). A mixture of ultrapure water with addition of 0.1% solution of formic acid (A) and acetonitrile (B) was used as a mobile phase. The gradient elution was carried out at constant flow 0.3 mL min−1 from 5% B (95% A) to 35% B 0–9 min, 2 min post time was performed to return to initial conditions. The injection volume was 4 μL and the column temperature was maintained at 35 °C. MassHunter workstation software in version B.08.00 was used for the control of the system, data acquisition, qualitative and quantitative analysis.

The optimization of the instrument conditions started from the proper tuning of Q-TOF detector in a positive mode with the use of Agilent ESI-L tuning mix in the extended dynamic range (2 GHz). The following instrument settings were applied: gas temp.: 250 °C, drying gas: 10 L/min, nebulizer pressure: 40 psig, capillary voltage: 1500 V, fragmentor voltage: 125 V, skimmer voltage: 65 V, octopole 1 RF voltage: 750 V.

Data acquisition was performed in centroids with the use of the TOF (MS) and auto tandem mass spectroscopy (MS/MS) mode. The spectral parameters for both modes were a mass range of 60–950 m/z and an acquisition rate of 1.5 spectra per s. To ensure accuracy in masses measurements, a reference mass correction was used, and masses 121.050873 and 922.009798 were used as lock masses.

Sample Preparation

The active substance was isolated from the tablets. For the pharmaceutical formulation of lacosamide, the average mass tablet was determined, and an equivalent of 1 mM lacosamide was transferred to a 10-mL volumetric flask containing 5 mL of water. After 5-min ultrasonic sweeping, the sample was diluted up to volume with water, and then centrifuged at 13,500 rpm for 5 min (at room temperature). This stock solution after adequate dilution was used for both HLM and photocatalytic experiments.

In Vitro Metabolism Study in HLM

Phase I metabolism reactions of lacosamide were studied in vitro with the use of human liver microsome fraction. Incubation system consisted of 0.05 mM substrate, 50 mM phosphate buffer (pH 7.4), and 0.5 mg/mL microsomes. HLM samples were pre-incubated at 37 °C for 2 min, and then, the metabolic reaction was initiated by addition of 10 μL NADPH (20 mM). Total volume of reaction suspension was 200 μL. The reaction was terminated after 30, 60, 90, 180, 270, and 360 min of incubation with 200 μL ice-cold acetonitrile–methanol mixture (1:1). Next, the precipitated samples were centrifuged at 13,500 rpm for 10 min at 4 °C, and the supernatants (50 μL) were transferred into autosampler vials for LC–ESI–HRMS analysis. The negative control samples were prepared as described above without addition of NADPH solution.

Photocatalytic Experiments

The photocatalytic reactions were performed in water solution with 0.025 mM lacosamide and 0.1 mg/mL TiO2. For all experiments, the formed suspensions were transferred into 3.5-mL quartz caped cells (l = 1 cm) and stirred in the dark at 500 rpm (microstirrer Cimarec, Telemodul, Thermo Electron LED GmbH, Germany) for 15 min to achieve adsorption–desorption equilibrium. Next, the reaction cells were mounted horizontally in an Atlas SUNTEST CPS+ photostability chamber with a D65 filter (Linsengericht, Germany and irradiated simultaneously with stirring. The irradiance was set to 750 W m2, which corresponds to energy dose of 2700 kJ/m2 h. The temperature in the chamber was controlled and kept below 35 °C. Aliquots (100 μL) were collected at proper intervals and time ranges 0–16 min. Suspensions were then centrifuged in the Eppendorf vials (MPW-375 centrifuge, MPW Med. Instruments, Poland) at 13,500 rpm for 5 min, 50 μL aliquots were collected, and UHPLC–ESI–HRMS analysis was performed.

Results and Discussion

Identification of Lacosamide Metabolites by Mass Spectrometry

In order to identify the structure of the lacosamide metabolites, HRMS analysis was performed with the use of auto MS/MS mode. Based on the obtained high-resolution spectra, 6 metabolites of lacosamide were found during this study (Table 1). Registered MS/MS spectra and fragmentation patterns of lacosamide and the detected products (M1–M6) were presented in Figures 17.

Table 1

Q-TOF accurate mass elemental composition and MS/MS fragmentation and of the analyzed substances

Comp.

No.
NameRetention

time (min)
Measured

mass [m/z]
Theoretical

mass [m/z]
Mass

error [ppm]
Molecular

formula [M + H]+
MS/MS fragm

[m/z]
Fragmentation ion

formula [M + H]+
Observed in

HLM TiO2
1Lacosamide3.85251.1382251.1390−3.18C13H19N2O3219.1119

209.1273

177.1008

144.0651

116.0704

108.0808

91.0546

74.0609
C12H15N2O2

C11H17N2O2

C10H13N2O

C6H10NO3

C5H10NO2

C7H10N

C7H7

C3H8NO
2M11.98209.1289209.12842.39C11H17N2O2164.1045

108.0802

91.0546

74.0596
C9H12N2O

C7H10N

C7H7

C3H8NO
XX
3M20.60146.0806146.0811−3.42C6H12NO3116.0707

100.0774

84.0815
C5H10NO2

C5H10NO

C5H10N
XX
4M32.58237.1200237.1233−13.92C12H17N2O3130.0497

108.0807

91.0542

60.0451
C5H8NO3

C7H10N

C7H7

C2H6NO
XX
5M42.10267.1313267.1339−9.73C13H18N2O4161.0918

144.0656

116.0704

107.0494

74.0608
C6H13N2O3

C6H10NO3

C5H10NO2

C7H7O

C3H8NO
X
6M52.50267.1337267.1339−0.74C13H18N2O4235.1070

225.1240

193.0956

144.0647

124.0756

116.0702

107.0493

74.0606
C12H15N2O3

C11H17N2O3

C10H13N2O2

C6H10NO3

C7H10NO

C5H10NO2

C7H7O

C3H8NO
X
7M63.20267.1340267.13390.37C13H18N2O4235.1076

225.1239

161.0920

144.0659

124.0758

107.0492

74.0612
C12H15N2O3

C11H17N2O3

C6H13N2O3

C6H10NO3

C7H10NO

C7H7O

C3H8NO
X
Figure 1.
Figure 1.

MS/MS spectrum and fragmentation pathway of lacosamide

Citation: Acta Chromatographica Acta Chromatographica 32, 2; 10.1556/1326.2019.00591

Figure 2.
Figure 2.

MS/MS spectrum and fragmentation pathway of M1

Citation: Acta Chromatographica Acta Chromatographica 32, 2; 10.1556/1326.2019.00591

Figure 3.
Figure 3.

MS/MS spectrum and fragmentation pathway of M2

Citation: Acta Chromatographica Acta Chromatographica 32, 2; 10.1556/1326.2019.00591

Figure 4.
Figure 4.

MS/MS spectrum and fragmentation pathway of M3

Citation: Acta Chromatographica Acta Chromatographica 32, 2; 10.1556/1326.2019.00591

Figure 5.
Figure 5.

MS/MS spectrum and fragmentation pathway of M4

Citation: Acta Chromatographica Acta Chromatographica 32, 2; 10.1556/1326.2019.00591

Figure 6.
Figure 6.

MS/MS spectrum and fragmentation pathway of M5

Citation: Acta Chromatographica Acta Chromatographica 32, 2; 10.1556/1326.2019.00591

Figure 7.
Figure 7.

MS/MS spectrum and fragmentation pathway of M6

Citation: Acta Chromatographica Acta Chromatographica 32, 2; 10.1556/1326.2019.00591

The spectra of M1–M3 metabolites were generated by the use of HLM, as well as with the photocatalytic method. The spectra of M4–M6 metabolites were generated from the photocatalytic experiment due to the inadequate quality of the spectrum obtained on microsomes.

As shown on the MS/MS spectrum of lacosamide (Figure 1), the fragmentation occurs in two ways due to the gradual degradation of the aliphatic chain with the formation of an ion with m/z 177.1008 (C10H13N2O). The fragment with m/z 108.0808 (C7H10N), which corresponds to phenylmethanaminium ion, is clearly marked. Fragments with m/z 144.0651 (C6H10NO3), 116.0704 (C5H10NO2), and 74.0609 (C3H8NO) indicates the further gradual decomposition of the aliphatic chain.

Metabolite M1 (m/z 209.1289, C11H17N2O2) was identified as a descarbonyl-lacosamide (Figure 2). Fragmentation gradually leads to N-methylethanamide ion (m/z 74.0596, C3H8NO) appearance, the most abundant structure in the spectrum. The ion with m/z 91.0546 (C7H7) identified as a phenylmethylium ion is also clearly marked.

The M2 metabolite (m/z 146.0806, C6H12NO3) was marked as a product of aliphatic chain detachment from the phenylmethanamine structure and specified as a N-(1-methoxy-3-oxopropan-2-yl)acetamide. Removal of the methoxy moiety results in the formation of an N-(1-oxopropan-2-yl)ethanaminium ion (m/z 116.0707, C5H10NO2). The cleavage of 2 oxygen atoms leads in turn to the formation of an ion with m/z 100.0774 (C5H10NO) and m/z 84.0815 (C5H10N) – the most abundant fragment in the spectrum which corresponds to N-ethenylprop-1-en-2-aminium ion (Figure 3).

Desmethyl lacosamide (M3) with m/z 237.1200 (C12H17N2O3) was found to be the third most abundant hepatic metabolite in our experiment (Figure 4). The ions with m/z 108.0807 (C7H10N) and m/z 91.0542 (C7H7) are the two most visible fragments in the spectrum, and they come from the gradual removal of the aliphatic chain from parent molecule. The most characteristic fragment with m/z 130.0497 (C5H8NO3) was found as a (2-acetamido-3-hydroxypropylidyne)oxidanium ion.

The M4–M6 metabolites were found to be the hydroxylated derivatives of lacosamide. M4 (m/z 267.1313, C13H18N2O4) was identified as 4-hydroxy-lacosamide (Figure 5). Characteristic fragment with m/z 107.0494 (C7H7O), which belong to the most abundant ion in fragmentation pattern, verifies the creation of (4-methylidenecyclohexa-2,5-dien-1-ylidene)oxidanium ion as a product of aliphatic chain detachment. Additional fragments with m/z 144.0656 (C13H18N2O4) and 116.0704 (C5H10NO2) indicate further degradation of the aliphatic part of the compound. M5 (m/z 267.1337, C13H18N2O4) was characterized as a 3-hydroxy-lacosamide. The presence of ions with m/z 144.0647 (C6H10NO3) and m/z 124.0756 (C7H10NO) with further creation of fragment with m/z 107.0493 (C7H7O) from (3-hydroxyphenyl)methylium ion indicates the preferred route for fragmentation of the compound (Figure 6). M6 (m/z 267.1340, C13H18N2O4) was identified as 2-hydroxy-lacosamide (Figure 7). Fragmentation in the case of this compound leads to gradual aliphatic chain degradation with creation ions with m/z 235.1076 (C12H15N2O3) and 225.1239 (C11H17N2O3). The most abundant in the spectrum is the fragment with m/z 107.0492 (C7H7O) identified as a (6-methylidenecyclohexa-2,4-dien-1-ylidene)oxidanium ion, which come from the second in turn m/z 124.0758 (C7H10NO). It should be noticed that M4–M6 metabolites were registered only on metabolic profiles obtained by photocatalytic approach. The use of this method allowed the verification of the presence of at least some trace amounts of these metabolites in given retention times on HLM profiles.

Evaluation of the Hepatic Lacosamide Metabolites Formation

In this study, only 3 metabolites from the hepatic pathway were obtained as a result of lacosamide incubation with the HLM fraction during 360 min (Figure 8). First of all, descarbonyl derivative (M1) was found to be a most abundant hepatic metabolite of lacosamide. The increase of this product in time is almost linear and grows up to the end of incubation. M2 metabolite, determined as a N-(1-methoxy-3-oxopropan-2-yl)acetamide appeared 60 min after the start of the experiment and reached higher values than M3 after 100 min. Formation kinetics of this metabolite is very similar to the main metabolite; however, its abundance is about twice lower. Desmethyl lacosamide (M3) appeared shortly after M1, reached maximum in the range of 90–270 min, and after that, its abundance apparently decreased. Its formation differs significantly from other metabolites (M1, M2) in both kinetic and quantitative terms, and it should be treated as a minor derivative in this case.

Figure 8.
Figure 8.

Evolution profiles of hepatic metabolites of lacosamide

Citation: Acta Chromatographica Acta Chromatographica 32, 2; 10.1556/1326.2019.00591

Pathways of Lacosamide Metabolism

Obtained results showed that lacosamide undergoes the three main metabolic pathways involving hepatocellular tissues. Deacetylation was found to be a preferred reaction type and facilitated the creation of M1 metabolite identified as a descarbonyl-lacosamide. The second most abundant derivative of lacosamide was characterized as a N-(1-methoxy-3-oxopropan-2-yl)acetamide (M2). It is a new transformation product, not described yet in the literature, of lacosamide, and its formation has been additionally verified by a photocatalytic process with the use of TiO2. Thus, its identification allowed the determination of the polar metabolic fraction of the test compound. The M3 product, which is a result of demethylation of lacosamide molecule, was found to be the third abundant metabolite. The Obtained results allow us to conclude that the formation of M4–M6 metabolites takes place with the participation of extrahepatic mechanisms, and their occurrence in urine may indicate renal metabolic pathway. Additionally, the hydroxylated and simultaneously desmethyled derivatives of lacosamide, described earlier in the literature [26], seem to indicate the complicity of the extrahepatic pathway in their origin. The proposed phase I hepatic metabolism pathway of lacosamide is shown in Figure 9.

Figure 9.
Figure 9.

The proposed hepatic metabolic pathway of lacosamide

Citation: Acta Chromatographica Acta Chromatographica 32, 2; 10.1556/1326.2019.00591

Conclusion

In this study complete phase I hepatic metabolism of lacosamide was proposed. With the use of UHPLC-ESI-HRMS a new, not described yet in the literature, polar metabolite of lacosamide-N-(1-methoxy-3-oxopropan-2-yl)acetamide was identified. This product was characterized as one of the two main metabolites and therefore, the necessity of its determination, especially in the case of the pharmacokinetic research or monitored therapies, should be considered.

Additionally, the results obtained with HLM were compared with those of photocatalytic techniques, which also made it possible to achieve the same transformation product. The combination of both techniques has found application in drug metabolism studies, and the photocatalytic method proved to be complementary to biological and enabled the rapid generation of metabolites, also unobtainable on the liver microsomes.

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  • 1.

    Ruiz-Garcia, A.; Bermejo, M.; Moss, A.; Casabo, V. G. J. Pharm. Sci. 2008, 97, 654.

  • 2.

    Costa, A.; Sarmento, B.; Seabra, V. Expert. Opin. Drug. Metab. Toxicol. 2014, 10, 103.

  • 3.

    Gómez-Lechón, M. J.; Castell, J. V.; Donato, M. T. Expert Opin. Drug Metab. Toxicol. 2008, 4, 837.

  • 4.

    Rautio, J.; Kumpulainen, H.; Heimbach, T.; Oliyai, R.; Oh, D.; Järvinen, T.; Savolainen, J. Nat. Rev. Drug. Discov. 2008, 7, 255.

  • 5.

    Kratz, F.; Müller, I. A.; Ryppa, C.; Warnecke, A. Chem. Med. Chem. 2008, 3, 20.

  • 6.

    Rooseboom, M.; Commandeur, J. N.; Vermeulen, N. P. Pharmacol. Rev. 2004, 56, 53.

  • 7.

    Remmer H. Am. J. Med. 1970, 49, 617.

  • 8.

    Almazroo, O. A.; Miah, M. K.; Venkataramanan, R. Clin. Liver. Dis. 2017, 21, 1.

  • 9.

    Fujishima, A.; Honda, K. Nature 1972, 238, 37.

  • 10.

    Gawlik, M.; Skibiński, R.; Trawiński, J.; Komsta, Ł. Acta Chromatogr. 2018, 30, 1.

  • 11.

    Ruokolainen, M.; Valkonen, M.; Sikanen, T.; Kotiaho, T.; Kostiainen, R. Eur. J. Pharm. Sci. 2014, 65, 45.

  • 12.

    Medana, C.; Calza, P.; Giancotti, V.; Dal Bello, F.; Pasello, E.; Montana, M.; Baiocchi, C. Drug Test. Anal. 2011, 3, 724.

  • 13.

    Gawlik, M.; Trawiński, J.; Skibiński, R. Eur. J. Pharm. Sci. 2018, 1, 391.

  • 14.

    Gawlik, M.; Skibiński, R. Int. J. Mass Spectrom. 2018, 433, 55.

  • 15.

    Fischer, R. S.; Acevedo, C.; Arzimanoglou, A., et al. Epilepsia 2014, 55, 475.

  • 16.

    Saha, R.; Mohapatra, S.; Kar, S. K.; Tekkalaki, B.; Anand, K. S. Intern. J. Epilepsy 2017, 4, 70.

  • 17.

    Hovinga C. A. Expert. Opin. Investig. Drugs 2002, 11, 1387.

  • 18.

    Greenaway, C.; Ratnaraj, N.; Sander, J. W.; Patsalos, P. N. Ther. Drug Monit. 2010, 32, 448.

  • 19.

    Choi, D.; Stables, J. P.; Kohn, H. J. Med. Chem. 1996, 39, 1907.

  • 20.

    Moavero, R.; Pisani, L. R.; Pisani, F.; Curatolo, P. Expert. Opin. Drug Saf. 2018, 17, 1015.

  • 21.

    Beyreuther, B. K.; Freitag, J.; Heers, C.; Krebsfänger, N.; Scharfenecker, U.; Stöhr, T. CNS Drug. Rev. 2007, 13, 21.

  • 22.

    Rogawski, M. A.; Tofighy, A.; White, H. S.; Matagne, A.; Wolff, C. Epilepsy Res. 2015, 110, 189.

  • 23.

    Errington, A. C.; Stöhr, T.; Heers, C.; Lees, G. Mol. Pharmacol. 2008, 73, 157.

  • 24.

    Doty, P.; Rudd, G. D.; Stoehr, T.; Thomas, D. Neurotherapeutics 2007, 4, 145.

  • 25.

    Cawello W. Clin. Pharmacokinet. 2015, 54, 901.

  • 26.

    Cawello, W.; Boekens, H.; Bonn, R. Eur. J. Drug. Metab. Pharmacokinet. 2012, 37, 241.

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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 27 0
Mar 2021 0 36 27
Apr 2021 0 34 5
May 2021 0 16 8
Jun 2021 0 5 7
Jul 2021 0 3 6
Aug 2021 0 0 0