Analysis of terizidone in plasma using HPLC-UV method and its application in a pharmacokinetic study of patients with drug-resistant tuberculosis.

Abstract

A chromatographic method has been developed and validated for the first time for analysis of terizidone in plasma. Terizidone was extracted from plasma by protein precipitation using a mixture of acetonitrile and methanol (1:1, v/v). The chromatographic separation was achieved with a gradient of acetonitrile and water both containing 0.1% formic acid on a Supelco Discovery® HS C18 (150 × 4.6 mm, 5 μm) reversed-phase column. Propranolol was used as the internal standard. The total run-time was 18 min. The calibration standard concentrations ranged between 3.125 and 200 μg/mL and calibration curves were linear with coefficient of determination values in the range of 0.9988-0.9999. The inter- and intra-day assay precision (percentage relative standard error) was <15% while mean accuracy was 107%. The mean extraction efficiencies of terizidone and IS were 76 and 89%, respectively. The validation results demonstrated that the method was selective and sensitive, and that terizidone was stable under the studied conditions. The method was successfully applied in a population pharmacokinetic study. The mean plasma concentration of terizidone in patients at all sampling time points was 51.8 ± 28 μg/mL. The method was simple, cheap and hence suitable for therapeutic drug monitoring of terizidone.