LC‐MS/MS method for the determination of agomelatine in human plasma and its application to a pharmacokinetic study

Abstract

A sensitive and selective LC-MS/MS method for the determination of agomelatine in human plasma was developed and validated. After simple liquid-liquid extraction, the analytes were separated on a Zorbax SB-C18 column (150 × 2.1 mm i.d., 5 µm) with an isocratic mobile phase consisting of 5 mm ammonium acetate solution (containing 0.1% formic acid) and methanol (30:70, v/v) at a flow-rate of 0.3 mL/min. The MS acquisition was performed in multiple reaction monitoring mode with a positive electrospray ionization source. The mass transitions monitored were m/z 244.1 → 185.3 and m/z 285.2 → 193.2 for agomelatine and internal standard, respectively. The methods were validated for selectivity, carry-over, matrix effects, calibration curves, accuracy and precision, extraction recoveries, dilution integrity and stability. The validated method was successfully applied to a pharmacokinetic study of agomelatine in Chinese volunteers following a single oral dose of 25 mg agomelatine tablet.

Effect of CYP1A2 polymorphism on the pharmacokinetics of agomelatine in Chinese healthy male volunteers

“…A pharmacokinetic study of agomelatine in Chinese has been reported, and the results of our study were in accordance with it. In our study, we also observed large interindividual variability of the pharmacokinetic parameters of agomelatine (C max from 0.43 to 71.2 ng/mL, AUC from 0.60 to 57.9 ng/mL·h).…”

Evaluation of agomelatine stability under different stress conditions using an HPLC method with fluorescence detection: application to the analysis of tablets and human plasma

“…At such wavelengths, it was possible to detect all degradation products of AGM. The use of fluorescence detection offers high sensitivity to the assay, making it an acceptable alternative to already existing sophisticated LC‐MS‐MS methods .…”

“…Another HPLC method with diode array detection and a gradient elution mode was applied to separate AGM from its potential impurities. Also, two LC‐MS/MS methods have been developed for the quantification of AGM in human plasma . A comparison between these previously reported methods for the analysis of AGM and the proposed method is presented in Table .…”

Bioequivalence and Pharmacokinetic Profiles of Agomelatine 25-mg Tablets in Healthy Chinese Subjects: A Four-Way Replicate Crossover Study Demonstrating High Intra- and Inter-Individual Variations

“…According to the available agomelatine pilot data, the sample size in the present study was estimated by referencing the literature by Chow et al 17) For determination of agomelatine in human plasma, an original LC-MS/MS method was developed and validated. Compared to the reported methods, 18,19) it was less time-consuming and had a wider range of quantification (0.05-20 ng/mL). The sampling scheme design was considered adequate for the determination of pharmacokinetic parameters with sufficient duration to fully assess the absorption and elimination phases of agomelatine.…”