Quantitative and qualitative application of a novel capillary microsampling device, Microsampling Wing™ (MSW), using antiepileptic drugs in rats

• Published in: Journal of pharmaceutical and biomedical analysis 2021-02, Vol.194, p.113788, Article 113788
• Main Authors: Hotta, Koichiro, Ishida, Tomomi, Noritake, Ken-ichi, Kita, Kenji, Mano, Yuji
• Format: Article
• Language: English
• Subjects: LC–MS/MS; Metabolite identification; Microsampling; Microsampling Wing; Pharmacokinetics
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2020.113788

[Display omitted] •This is the first report to evaluate a novel microsampling device, namely, MSW.•A PK study and metabolite identification of AEDs in rats were conducted.•The plasma drug levels in MSW were similar to those obtained using a glass capillary.•Metabolites of carbamazepine were successfully identified in plasma.•MSW is a useful microsampling device for both PK and Met-ID in rats. A novel microsampling device, namely, the Microsampling Wing™ (MSW), was evaluated using three anti-epileptic drugs (AEDs): carbamazepine, lamotrigine, and phenytoin. A simultaneous assay method of the three AEDs was developed and qualified via liquid chromatography with tandem mass spectrometry. Using 2.8 μL plasma, the three AEDs were quantifiable from 1 or 2 ng/mL. According to the intra-assay reproducibility assessment and additional validation parameters, the established method is reproducible. To apply the device to a pharmacokinetic (PK) study in rats, a cocktail of the three AEDs was orally administered to rats. Whole blood samples were serially collected using the MSW device and a glass capillary from the tail vein, and plasma samples (each 2.8 μL) from each device were assayed to compare PK parameters. The PK parameters of the three AEDs were similar between the two devices. A metabolite identification study was also conducted after oral administration of carbamazepine to rats. At least seven metabolites were detected in plasma, and the major metabolite was carbamazepine 10,11-epoxide, which is in accordance with the reported results. These findings suggest that the MSW device is a useful microsampling device for PK and metabolite identification studies.