Simultaneous determination of clevidipine and its major metabolite H152/81 in rat plasma by LC-MS/MS / 中国药学杂志

ABSTRACT

OBJECTIVE: To develop an LC-MS/MS method for simultaneous determination of clevidipine and its major metabolite H152/81 concentration in rat plasma. METHODS: The plasma samples were processed with liquid-liquid extraction, with nimo-dipin as an internal standard. The separation was achieved on ZORBAX SB C18 column (2.1 mm×100 mm, 3.5 μm) and eluted with linear gradient using acetonitrile and 0.1% formic acid at the flow rate of 0.3 mL·min-1, the injection volume was 10 μL and the column temperature was maitained at 30℃. The total time of the analysis was 3.5 min. Detection of the analytes were achieved using positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. RESULTS: The linear calibration curve of clevidipine and its major metabolite H152/81 were obtained concentration range of 1.0-200 μg·L-1 (r>0.99), with the lower limit of quantitation (LLOQ) of 1.0 μg·L-1. The average recovery was between 92.5%-109.8%, Intra-day and inter-day relative standard deviations were both below 15%. The recoveries of low, middle and high concentrations were 71.3%-82.6%, respectively. CONCLUSION: The established method is rapid, sensitive, accurate, specific and reliable, and suitable for simultaneous determination of clevidipine and its major metabolite H152/81 in rat plasma.