Analysis of nifedipine in human plasma and amniotic fluid by liquid chromatography-tandem mass spectrometry and its application to clinical pharmacokinetics in hypertensive pregnant women

•A LC-MS/MS method was developed and validated to analyze nifedipine in human plasma and amniotic fluid.•The complete development and validation of nifedipine analysis is described for the first time in amniotic fluid.•This is the most sensitive method of nifedipine analysis in human plasma and amniotic fluid.•Both methods use low biological sample volumes and simple sample preparation.

Nifedipine is a dihydropyridine calcium channel blocker used for the treatment of hypertension in pregnant women. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for analysis of nifedipine in human plasma and amniotic fluid. Separation of nifedipine and nitrendipine (IS) was performed using a LiChroCART® RP-Select B column and a mixture of water:acetonitrile:glacial acetic acid (30:70:0.5 v/v) as the mobile phase. Aliquots of 500 μL of biological samples were extracted at pH 13 using dichloromethane:n-pentane (3:7 v/v). The validated method was applied to a study of the pharmacokinetics of nifedipine in human plasma and amniotic fluid samples collected up to 12 h after administration of the last slow-release nifedipine (20 mg/12 h) dose to 12 hypertensive pregnant women. The estimated pharmacokinetic parameters of nifedipine showed a mean AUC0-12 of 250.2 ng h/mL, ClT/F of 89.2 L/h, Vd/F of 600.0 L and t1/2 5.1 h. The mean amniotic fluid/plasma concentration ratio was 0.05. The methods proved to be highly sensitive by showing a lower quantification limit of 0.1 ng/mL for both matrices. And this study reports for the first time the complete development and validation of the method to quantify nifedipine in amniotic fluid using LC-MS-MS.