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 C (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.

Amount of Cycloserine Emanating from Terizidone Metabolism and Relationship with Hepatic Function in Patients with Drug-Resistant Tuberculosis

“…The lower limit of quantification was 3.125 µg/mL, while the limit of detection was 0.78 µg/mL. The coefficient of determination value ranged between 0.9988 and 0.9999, and calibration curves were linear [21].…”

Steady‐state population pharmacokinetics of terizidone and its metabolite cycloserine in patients with drug‐resistant tuberculosis

“…Calibration curves were linear with coefficient of determination ranging between 0.9988 and 0.9999. The lower limit of quantification and limit of detection was 3.125 and 0.78 μg mL −1 , respectively . Cycloserine concentrations were analysed using ultra‐performance liquid chromatography–tandem mass spectrometry method and validated according to the international guidelines .…”

Impurity Profiling of First Line Anti-Tb Drug-Terizidone Using Chromatographic and Related Techniques

“…The extensive literature survey shows several reported methods which are; UV method [4], HPLC method for TRZ in plasma [5], stability study for TRZ [6] (degradation products were not separated nor reported), the two degradation products of TRZ are reported by HPTLC and MS/MS method [7] (the DPs are marked with an asterisk in paper and cited which are reported in literature), HPTLC and LC/MS/MS methods are reported [8]. None of the reported literature investigates the entire impurity profile for TRZ, therefore it was an opportunity and challenge to study stress degradation and report the impurity profile of TRZ.…”