Determination of nifedipine in human plasma by ultra performance liquid chromatography–tandem mass spectrometry and its application in a pharmacokinetic study

A fast, sensitive and selective ultra performance liquid chromatography–tandem mass spectrometric (UPLC–MS/MS) method was developed for the determination of nifedipine in human plasma. Nitrendipine was used as the internal standard. The sample preparation employed liquid–liquid extraction with a mixture of n-hexane–diethyl ether (1:3, v/v). Chromatographic separation was performed on an ACQUITY UPLC™ BEH C18 column. The mobile phase was composed of acetonitrile–10 mmol/L ammonium acetate (75:25, v/v) with a flow rate of 0.20 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. A high throughput was achieved with a run time of 1.4 min per sample. The linear calibration curves were obtained in the concentration range of 0.104–52.0 ng/mL (r2 ≥ 0.99) with a lower limit of quantification (LLOQ) of 0.104 ng/mL. The intra- and inter-day precision (relative standard deviation, RSD) values were below 15% and the accuracy (relative error, RE) was −4.0% to 6.2% at three quality control levels. The method was fully validated and successfully applied to a clinical pharmacokinetic study of nifedipine sustained-release tablet in healthy male volunteers.