Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Method Development and Validation of a Novel UHPLC Coupled with MS/MS System for the Estimation of Brivaracetam in Human (K2EDTA) Plasma Samples and its Application to Pharmacokinetic Study

Author(s): Kiran Kumar Aalapati *, Amit Singh and Ranjana S. Patnaik

Volume 18, Issue 5, 2022

Published on: 28 June, 2021

Page: [504 - 512] Pages: 9

DOI: 10.2174/1573412917666210503113118

Price: $65

Abstract

Background: Brivaracetam is a novel antiepileptic drug clinically approved for the treatment of partial onset seizures in adults and adolescents. It has some abuse potential and assigns to Schedule V category under the Controlled Substance Act by the Drug Enforcement Administration. It is essential to develop a faster, simple, and highly sensitive method for the quantification of Brivaracetam in human plasma by employing simple liquid-liquid extraction.

Objective: The objective of this study is to develop and validate a novel UHPLC-MS/MS method for the estimation of brivaracetam in human plasma samples and application to pharmacokinetic study.

Methods: An ultra-high-pressure liquid chromatography-tandem mass spectrometry method was developed and validated according to current regulatory guidelines for bioanalytical methods. Sample processing (50 μL) involved only a simple liquid-liquid extraction by ethyl acetate as extraction solvent. Brivaracetam-d7 was used as an internal standard. The chromatographic analysis was performed by a Unisol C18 (4.6 X 100 mm, 5μm) column using 0.1% formic acid in water/acetonitrile (20/80 V/V) as an isocratic mobile phase, at a flow rate of 1.0 mL/min with a run time of 2.2 min. Brivaracetam and its internal standard Brivaracetam D7 were detected and quantified in positive ion mode using multiple reaction monitoring transitions at m/z 213.100→168.100 and m/z 220.000→175.100, respectively. The developed method was applied to assess pharmacokinetic parameters like Cmax, Tmax, t1/2 and AUC for Brivaracetam in healthy, male, and adult humans.

Results: The method was validated over a concentration range of 20.000 ng/mL to 4000. 000 ng/mL. Both intra- and inter-assay precision and accuracy were <15% for all quality control samples. No matrix effect was observed. Pharmacokinetic results showed that test formulation is bioequivalent with reference formulation.

Conclusion: The present assay is faster, highly sensitive and simpler than previously published analytical reports for brivaracetam in human plasma samples and is suitable for pharmacokinetic evaluation of any marketed formulation.

Keywords: Brivaracetam, Liquid-Liquid Extraction (LLE), UHPLC, MS/MS, Bioanalytical Method Validation, Pharmacokinetics.

« Previous Next »
Graphical Abstract

[1]
Klein, P.; Diaz, A.; Gasalla, T.; Whitesides, J. A review of the pharmacology and clinical efficacy of brivaracetam. Clin. Pharmacol., 2018, 10, 1-22.
[http://dx.doi.org/10.2147/CPAA.S114072] [PMID: 29403319]
[2]
Klitgaard, H.; Matagne, A.; Nicolas, J.M.; Gillard, M.; Lamberty, Y.; De Ryck, M.; Kaminski, R.M.; Leclercq, K.; Niespodziany, I.; Wolff, C.; Wood, M.; Hannestad, J.; Kervyn, S.; Kenda, B. Brivaracetam: Rationale for discovery and preclinical profile of a selective SV2A ligand for epilepsy treatment. Epilepsia, 2016, 57(4), 538-548.
[http://dx.doi.org/10.1111/epi.13340] [PMID: 26920914]
[3]
Patsalos, P.N.; Spencer, E.P.; Berry, D.J. Therapeutic drug monitoring of antiepileptic drugs in epilepsy. A 2018 update. Ther. Drug Monit., 2018, 40(5), 526-548.
[http://dx.doi.org/10.1097/FTD.0000000000000546] [PMID: 29957667]
[4]
Moseley, B.D.; Chanteux, H.; Nicolas, J. M.; Laloyaux, C.; Gidal, B.; Stockis, A. A review of the drug-drug interactions of the antiepileptic drug brivaracetam. Epilep. Res., 2020, 163 art. no. 106327
[5]
Moseley, B.D.; Otoul, C.; Staelens, L.; Stockis, A. Pharmacokinetic interaction of brivaracetam on other antiepileptic drugs in adults with focal seizures: Pooled analysis of data from randomized clinical trials. Epilep. Res, 2019, 158 art. no. 106218
[6]
US Food and Drug Administration Brivaracetam. 2016. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=205836
[7]
Gillard, M.; Fuks, B.; Leclercq, K.; Matagne, A. Binding characteristics of brivaracetam, a selective, high affinity SV2A ligand in rat, mouse and human brain: relationship to anti-convulsant properties. Eur. J. Pharmacol., 2011, 664(1-3), 36-44.
[http://dx.doi.org/10.1016/j.ejphar.2011.04.064] [PMID: 21575627]
[8]
Kasteleijn-Nolst Trenité, D.G.; Genton, P.; Parain, D.; Masnou, P.; Steinhoff, B.J.; Jacobs, T.; Pigeolet, E.; Stockis, A.; Hirsch, E. Evaluation of brivaracetam, a novel SV2A ligand, in the photosensitivity model. Neurology, 2007, 69(10), 1027-1034.
[http://dx.doi.org/10.1212/01.wnl.0000271385.85302.55] [PMID: 17785672]
[9]
Biton, V.; Berkovic, S.F.; Abou-Khalil, B.; Sperling, M.R.; Johnson, M.E.; Lu, S. Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults: a phase III randomized, double-blind, placebo-controlled trial. Epilepsia, 2014, 55(1), 57-66.
[http://dx.doi.org/10.1111/epi.12433] [PMID: 24446953]
[10]
Rolan, P.; Sargentini-Maier, M.L.; Pigeolet, E.; Stockis, A. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after multiple increasing oral doses in healthy men. Br. J. Clin. Pharmacol., 2008, 66(1), 71-75.
[http://dx.doi.org/10.1111/j.1365-2125.2008.03158.x] [PMID: 18341673]
[11]
Sargentini-Maier, M.L.; Rolan, P.; Connell, J.; Tytgat, D.; Jacobs, T.; Pigeolet, E.; Riethuisen, J.M.; Stockis, A. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after single increasing oral doses in healthy males. Br. J. Clin. Pharmacol., 2007, 63(6), 680-688.
[http://dx.doi.org/10.1111/j.1365-2125.2006.02829.x] [PMID: 17223857]
[12]
Sargentini-Maier, M.L.; Espié, P.; Coquette, A.; Stockis, A. Pharmacokinetics and metabolism of 14C-brivaracetam, a novel SV2A ligand, in healthy subjects. Drug Metab. Dispos., 2008, 36(1), 36-45.
[http://dx.doi.org/10.1124/dmd.107.017129] [PMID: 17908923]
[13]
Abram, M.; Jakubiec, M.; Kamiński, K. Chirality as an Important Factor for the Development of New Antiepileptic Drugs. ChemMedChem, 2019, 14(20), 1744-1761.
[http://dx.doi.org/10.1002/cmdc.201900367] [PMID: 31476107]
[14]
Qiu, S. Kourosch Abbaspour Tehrani.; Sergey Sergeyev.; Patrick Bultinck.; Wouter Herrebout.; Benoit Mathieu. Stereochemistry of the Brivaracetam Diastereoisomers. Chiral., 2016, 28(3), 215-225.
[http://dx.doi.org/10.1002/chir.22558]
[15]
Iqbal, M.; Ezzeldin, E.; Al-Rashood, K.A. UPLC-MS/MS assay for identification and quantification of brivaracetam in plasma sample: Application to pharmacokinetic study in rats. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1060, 63-70.
[http://dx.doi.org/10.1016/j.jchromb.2017.05.039] [PMID: 28600961]
[16]
Atul Vasanth, D.; Rajkamal, B. A Validated LC-MS/MS method for pharmacokinetic study of Brivaracetam in healthy rabbits. Int. J. Pharm. Pharm. Sci., 2018, 10(2), 24-29.
[http://dx.doi.org/10.22159/ijpps.2018v10i2.21457]
[17]
Stockis, A.; Hartstra, J.; Mollet, M.; Hadi, S. Bioavailability and bioequivalence comparison of brivaracetam 10, 50, 75, and 100 mg tablets and 100 mg intravenous bolus. Epilepsia, 2016, 57(8), 1288-1293.
[http://dx.doi.org/10.1111/epi.13433] [PMID: 27346728]
[18]
Otoul, C.; Watanabe, S.; McCabe, S.; Stockis, A. Relative bioavailability and bioequivalence of Brivaracetam 10 mg/mL oral solution and 50-mg-fim-coated tablet. Clin. Pharmacol. Drug Dev., 2017, 6(3), 313-317.
[http://dx.doi.org/10.1002/cpdd.275] [PMID: 27274002]
[19]
Mohamed, S.; Riva, R.; Contin, M. Development and Validation of an UHPLC-MS/MS Assay for the Therapeutic Monitoring of Brivaracetam Plasma Concentrations in Patients with Epilepsy. Ther. Drug Monit., 2020, 42(3), 445-451.
[http://dx.doi.org/10.1097/FTD.0000000000000726] [PMID: 31934942]
[20]
Bhamare, P.; Umadoss, P.; Upmanyu, N.; Dubey, R. Identification, isolation, structural characterisation, synthesis and: In silico toxicity prediction of the alkaline hydrolytic degradation product of brivaracetam by using LC-PDA, preparative HPLC, LC/HESI/LTQ, FTIR, and 1H NMR. Anal. Methods, 2020, 12, 1868-1881.
[http://dx.doi.org/10.1039/C9AY02582K]
[21]
Bourgogne, E.; Culot, B.; Dell’Aiera, S.; Chanteux, H.; Stockis, A.; Nicolas, J.M. Off-line solid phase extraction and liquid chromatography-tandem mass spectrometry method for the quantitation of brivaracetam acid metabolites: Method validation and application to in vitro metabolism assays. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2018, 1086, 138-145.
[http://dx.doi.org/10.1016/j.jchromb.2018.04.018] [PMID: 29665472]
[22]
Guidance for Industry; Bioanalytical Method Validation, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Veterinary Medicine (CVM); , 2018.
[23]
Pilli, N.R.; Narayanasamy, S.; Xu, L.; Chockalingam, A.; Shea, K.I.; Stewart, S.; Rouse, R.; Patel, V.; Matta, M.K. A high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in Sprague Dawley rats. RSC Advances, 2020, 10, 886-896.
[http://dx.doi.org/10.1039/C9RA05785D]
[24]
Narayanasamy, S.; Pilli, N.R.; Xu, L.; Chockalingam, A.; Shea, K.I.; Stewart, S.; Patel, V.; Rouse, R.; Matta, M.K. An alternating polarity switching assay for quantification of oxycodone and topiramate: An application of LC-MS/MS method in support to PK/PD study in rodents. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2019, 1118-1119, 93-100.
[http://dx.doi.org/10.1016/j.jchromb.2019.04.044] [PMID: 31030106]

Rights & Permissions Print Cite
Article Metrics
19
1
© 2024 Bentham Science Publishers | Privacy Policy