Validation of Conversion Factors for Therapeutic Drug Monitoring of Lacosamide, Lamotrigine, and Levetiracetam in Dried Capillary Blood

Abstract

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An LC-MS/MS Method for Quantification of Lamotrigine and Its Main Metabolite in Dried Blood Spots

“…Our objective was to develop and validate a method for quantification of LTG and its main metabolite, LTG-N2-GLU, in DBS samples that combines the advantages of the DBS sampling technique and the LC-MS/MS method in terms of sensitivity, selectivity, and short analysis run time. Although several LC-MS/MS methods for lamotrigine quantitation in DBS samples exist that offer either a superior sensitivity [ 39 ] or include multiple other antiepileptic drugs [ 38 , 39 , 40 , 41 , 42 , 44 , 46 , 47 , 48 ], none of them offers the capability of simultaneous measurement of both LTG and LTG-N2GLU. During the optimization of sample preparation, preliminary experiments were performed with the HPLC-UV method that was used for the analysis of plasma samples, with some minor modifications.…”

“…9, who took the same 400 mg/day dose, pointing to significantly induced metabolic clearance in subject nr. 4, likely due to the phenytoin-induced UGT enzyme activity [ 48 ]. Other antiepileptic drugs could also interfere with LTG pharmacokinetics, but they were not present in our study population.…”

“…Till present, several analytical methods have been reported for the analysis of LTG and/or its main metabolite in plasma or serum samples [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ] as well as in dried blood [ 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]; however, there were no methods for the determination of lamotrigine together with its main metabolite in DBS. We consider the latter highly valuable for identifying the reasons for the changed LTG clearance in patients with sub- or supra-therapeutic plasma levels.…”

“…Therefore, for the development of analytical methods for TDM by using DBS samples, it is necessary to overcome some major obstacles for their routine implementation [9]. Till present, several analytical methods have been reported for the analysis of LTG and/or its main metabolite in plasma or serum samples as well as in dried blood [38][39][40][41][42][43][44][45][46][47][48]; however, there were no methods for the determination of lamotrigine together with its main metabolite in DBS. We consider the latter highly valuable for identifying the reasons for the changed LTG clearance in patients with sub-or supra-therapeutic plasma levels.…”