A validated chiral LC method for the determination of Zolmitriptan and its potential impurities.

摘要

A new, accurate and reliable chiral HPLC method was developed for the determination of Zolmitriptan, (4S)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl] methyl]-2-oxazolidinone an antimigraine agent and its potential impurities namely (4R)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl] methyl]-2-oxazolidinone [(R)-enantiomer] and (4S)-4-(4-aminobenzyl)-2-oxazolidinone (Imp-1) in pharmaceutical formulations and in bulk drugs. HPLC separation was carried out by normal phase chromatography with a mobile phase composed of hexane:isopropanol:methanol:diethylamine in the ratio (75:10:15:0.1, v/v/v/v) pumped at a flow rate of 1.0ml/min on a Chiralpak AD-H column. Zolmitriptan and its potential impurities were baseline resolved in the optimized method. The presence of diethylamine in the mobile phase has played a key role in achieving chromatographic resolution between the enantiomers and also in enhancing chromatographic efficiency. The developed method was also found to be selective under exposed conditions UVlight and 60 degrees C. The developed method was completely validated and proved to be robust. The values of the limit of detection (LOD) and limit of quantification (LOQ) of (R)-enantiomer and Imp-1 were 100, 250ng/ml and 30, 1000ng/ml, respectively, for 10mul injection volume. The validated method yielded good results regarding selectivity, linearity, precision, accuracy and ruggedness. Zolmitriptan sample solution and mobile phase are found to be stable for at least 24h. The proposed method was found to be suitable and accurate for the quantitative determination of Zolmitriptan and its impurities namely (R)-enantiomer and Imp-1 in bulk drugs and commercial formulations.