Generic placeholder image

Current Pharmaceutical Analysis

Editor-in-Chief

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

Opinion Article

Comparison of HPLC-DAD and UPLC-MS/MS in Monitoring Serum Concentration of Lamotrigine

Author(s): Xubin Wang, Zhibin Chen , Xiaofang Ke, Yingying Wang, Lufeng Hu* and Congrong Tang*

Volume 18, Issue 5, 2022

Published on: 13 January, 2022

Page: [449 - 454] Pages: 6

DOI: 10.2174/1573412917666210215150712

Price: $65

Abstract

Background: Lamotrigine (LTG) is a broad-spectrum and first-line anti-epileptic drug. To monitor the serum levels of LTG in epileptic seizures patients, high-performance liquid chromatography with diode-array detection (HPLC-DAD) and ultra-performance liquid chromatography-- tandem mass spectrometry (UPLC-MS/MS) methods were established and compared.

Methods: Imatinib was used as the internal standard (IS) for both methods. LTG and IS were detected at 246 nm by HPLC-DAD. In UPLC-MS/MS, LTG and IS positive ion were detected by multiple reaction monitoring (MRM), with m/z of 256/210.9 and 494/394.02, respectively. A total of 37 blood samples from epileptic patients were determined and studied by these two methods.

Results: There was an acceptable linearity for the two methods. The concentration range of LTG was 0.59 ~ 22.20 mg/L by HPLC, and 0.28 ~ 23.97 mg/L by UPLC-MS/MS. The Pearson regression coefficient of Deming regression was 0.9653 (95% CI: 0.9332 to 0.9821). Bland–Altman method demonstrated that the concentration of LTG determined by UPLC-MS/MS was 8.3% higher than that determined by HPLC (limits of agreement, -32.0% to +48.6%).

Conclusion: There was a significant correlation between the two methods. Both HPLC and UPLC- MS/MS can be used for routine clinical monitoring of LTG.

Keywords: Lamotrigine, HPLC, UPLC-MS/MS, determination, serum, precipitation.

Next »
Graphical Abstract
[1]
LaRoche, S.M.; Helmers, S.L. The new antiepileptic drugs - Clinical applications. JAMA, 2004, 291(5), 615-620.
[2]
Trankner, A.; Sander, C.; Schonknecht, P. A critical review of the recent literature and selected therapy guidelines since 2006 on the use of lamotrigine in bipolar disorder., 2013.
[3]
Froscher, W.; Keller, F.; Vogt, H.; Kramer, G. Prospective study on concentration-efficacy and concentration-toxicity: correlations with lamotrigine serum levels. Epileptic Disord., 2002, 4(1), 49-55.
[4]
Seo, H.J.; Chiesa, A.; Lee, S.J.; Patkar, A.A.; Han, C.; Masand, P.S.; Serretti, A.; Pae, C.U. Safety and tolerability of lamotrigine: results from 12 placebo-controlled clinical trials and clinical implications. Clin. Neuropharmacol., 2011, 34(1), 39-47.
[5]
Clark, C.T.; Klein, A.M.; Perel, J.M.; Helsel, J.; Wisner, K.L. Lamotrigine dosing for pregnant patients with bipolar disorder. Am. J. Psychiatry, 2013, 170(11), 1240-1247.
[6]
Milosheska, D.; Lorber, B.; Vovk, T.; Kastelic, M.; Dolzan, V.; Grabnar, I. Pharmacokinetics of lamotrigine and its metabolite N-2-glucuronide: Influence of polymorphism of UDP-glucuronosyltransferases and drug transporters. Br. J. Clin. Pharmacol., 2016, 82(2), 399-411.
[7]
Brzakovic, B.B.; Vezmar Kovacevic, S.D.; Vucicevic, K.M.; Miljkovic, B.R.; Martinovic, Z.J.; Pokrajac, M.V.; Prostran, M.S. Impact of age, weight and concomitant treatment on lamotrigine pharmacokinetics. J. Clin. Pharm. Ther., 2012, 37(6), 693-697.
[8]
Johannessen, S.I.; Battino, D.; Berry, D.J.; Bialer, M.; Kramer, G.; Tomson, T.; Patsalos, P.N. Therapeutic drug monitoring of the newer antiepileptic drugs. Ther. Drug Monit., 2003, 25(3), 347-363.
[9]
Tai, S.S.C.; Yeh, C.Y.; Phinney, K.W. Development and validation of a reference measurement procedure for certification of phenytoin, phenobarbital, lamotrigine, and topiramate in human serum using isotope-dilution liquid chromatography/tandem mass spectrometry. Anal. Bioanal. Chem., 2011, 401(6), 1915-1922.
[10]
Westley, I.S.; Morris, R.G. Seradyn quantitative microsphere system lamotrigine immunoassay on a Hitachi 911 analyzer compared with HPLC-UV. Ther. Drug Monit., 2008, 30(5), 634-637.
[11]
Baldelli, S.; Castoldi, S.; Charbe, N.; Cozzi, V.; Fucile, S.; Cattaneo, D.; Clementi, E. Comparison of the QMS analyzer with HPLC-UV for the quantification of lamotrigine concentrations in human plasma samples. Ther. Drug Monit., 2015, 37(5), 689-694.
[12]
Greiner-Sosanko, E.; Giannoutsos, S.; Lower, D.R.; Virji, M.A.; Krasowski, M.D. Drug monitoring: Simultaneous analysis of lamotrigine, oxcarbazepine, 10-hydroxycarbazepine, and zonisamide by HPLC-UV and a rapid GC method using a nitrogen-phosphorus detector for levetiracetam. J. Chromatogr. Sci., 2007, 45(9), 616-622.
[13]
Serralheiro, A.; Alves, G.; Fortuna, A.; Rocha, M.; Falcao, A. First HPLC-UV method for rapid and simultaneous quantification of phenobarbital, primidone, phenytoin, carbamazepine, carbamazepine-10,11-epoxide, 10,11-trans-dihydroxy-10,11-dihydrocarbamazepine, lamotrigine, oxcarbazepine and licarbazepine in human plasma. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2013, 925, 1-9.
[14]
Contin, M.; Mohamed, S.; Candela, C.; Albani, F.; Riva, R.; Baruzzi, A. Simultaneous HPLC-UV analysis of rufinamide, zonisamide, lamotrigine, oxcarbazepine monohydroxy derivative and felbamate in deproteinized plasma of patients with epilepsy. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2010, 878(3-4), 461-465.
[15]
Ferreira, A.; Rodrigues, M.; Falcao, A.; Alves, G. A rapid and sensitive HPLC-DAD assay to quantify lamotrigine, phenytoin and its main metabolite in samples of cultured HepaRG cells. J. Chromatogr. Sci., 2016, 54(8), 1352-1358.
[16]
Matar, K.M.; Nicholls, P.J.; Bawazir, S.A.; al-Hassan, M.I.; Tekle, A. A rapid liquid chromatographic method for the determination of lamotrigine in plasma. J. Pharm. Biomed. Anal., 1998, 17(3), 525-531.
[17]
Ventura, S.; Rodrigues, M.; Pousinho, S.; Falcão, A.; Alves, G. Determination of lamotrigine in human plasma and saliva using microextraction by packed sorbent and high performance liquid chromatography–diode array detection: An innovative bioanalytical tool for therapeutic drug monitoring. Microchem. J., 2017, 130, 221-228.
[18]
Hotha, K.K.; Kumar, S.S.; Bharathi, D.V.; Venkateswarulu, V. Rapid and sensitive LC-MS/MS method for quantification of lamotrigine in human plasma: application to a human pharmacokinetic study. Biomed. Chromatogr., 2012, 26(4), 491-496.
[19]
Linder, C.; Andersson, M.; Wide, K.; Beck, O.; Pohanka, A. A LC-MS/MS method for therapeutic drug monitoring of carbamazepine, lamotrigine and valproic acid in DBS. Bioanalysis, 2015, 7(16), 2031-2039.
[20]
Juenke, J.M.; Miller, K.A.; Ford, M.A.; McMillin, G.A.; Johnson-Davis, K.L. A comparison of two FDA approved lamotrigine immunoassays with ultra-high performance liquid chromatography tandem mass spectrometry. Clin. Chim. Acta, 2011, 412(19-20), 1879-1882.
[21]
Namdev, K.K.; Dwivedi, J.; Chilkoti, D.C.; Sharma, S. A simple, rapid and stability indicating validated method for quantification of lamotrigine in human plasma and dry plasma spot using LC-ESI-MS/MS: Application in clinical study. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2018, 1072, 362-369.
[22]
Itabashi, S.; Bito, R.; Nishina, M.; Fukumoto, M.; Soda, M.; Doi, M.; Usui, S.; Kitaichi, K. Determination of lamotrigine in human plasma using liquid chromatography-tandem mass spectrometry. Neuropsychopharmacol Rep., 2019, 39(1), 48-55.
[23]
Ghatol, S.; Vithlani, V.; Gurule, S.; Khuroo, A.; Monif, T.; Partani, P. Liquid chromatography tandem mass spectrometry method for the estimation of lamotrigine in human plasma: Application to a pharmacokinetic study. J. Pharm. Anal., 2013, 3(2), 75-83.
[24]
Shah, H.J.; Subbaiah, G.; Patel, D.M.; Suhagia, B.N.; Patel, C.N. Rapid quantification of lamotrigine in human plasma by two LC systems connected with tandem MS. J. Chromatogr. Sci., 2010, 48(5), 375-381.
[25]
Linder, C.; Hansson, A.; Sadek, S.; Gustafsson, L.L.; Pohanka, A. Carbamazepine, lamotrigine, levetiracetam and valproic acid in dried blood spots with liquid chromatography tandem mass spectrometry; method development and validation. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2018, 1072, 116-122.
[26]
Zufia, L.; Ibanez, N.; Aldaz, A. Comparison between lamotrigine plasma concentrations measured by QMS immunoassay on CDx-90 autoanalyzer and by HPLC. Ther. Drug Monit., 2011, 33(4), 521-522.
[27]
Morgan, P.E.; Fisher, D.S.; Evers, R.; Flanagan, R.J. A rapid and simple assay for lamotrigine in serum/plasma by HPLC, and comparison with an immunoassay. Biomed. Chromatogr., 2011, 25(7), 775-778.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy