Direct chiral separation of troglitazone stereoisomers using reversed-phase high-performance liquid chromatography.
A simple HPLC method for the direct chiral separation of troglitazone stereoisomers was developed. The separation was performed on a reversed-phase cellulose-derivertized chiral column (Chiralcel OJ-R) using a mobile phase consisting of methanol-acetic acid (1000:1, v/v) at a flow rate of 0.5 ml/min. The peak areas of stereoisomers separated from 0.13 to 0.75 mg/ml of troglitazone had good linearity, with correlation coefficients > 0.999 in the reversed-phase mode. The repeatability of the ratios of stereoisomers isolated from 0.5 mg/ml of troglitazone had a relative standard deviation of 0.1-0.2%. The relative sensitivities of the four isomers at UV 285 nm were similar, as each response factor was within the range of 0.99-1.01. Troglitazone racemized at the chiral center of the thiazolidine ring in methanol solution, but was found to be stable for 24 h in methanol-acetic acid (1000:1, v/v). This method was applied to the stereoisomeric analysis of troglitazone in pharmaceutical formulations and used to evaluate the constancy of the stereoisomer ratio in the manufacturing process and stability testing.
D002626:Chemistry, Pharmaceutical; D002839:Chromans / Q000032:analysis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015203:Reproducibility of Results; D013237:Stereoisomerism; D013844:Thiazoles / Q000032:analysis* / Q000737:chemistry; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone