A novel UPLC-MS/MS method for the quantification of nifedipine and its application to a pharmacokinetic study in healthy Chinese volunteers

Abstract Nifedipine, a representative calcium antagonist, is one of the first-line drugs for the treatment of hypertension, angina pectoris and cardiovascular disease, and its sustained-or controlled-release formulations are commonly used in clinical practice. Notably, nifedipine exhibits extreme photosensitivity, which displays a significant challenge to the analysis of biological samples. For the first time, the current study established a simple, rapid, and sensitive LC-MS/MS method for the quantification of nifedipine in human plasma, which employs protein precipitation as the pretreatment procedure to minimize sample manipulation. Nifedipine was separated on a Poroshell 120 SB-C18 column (2.1 × 50 mm, 2.7 µm) column with gradient elution using acetonitrile and 10 mM ammonium acetate containing 0.2% formic acid. The chromatographic runtime for each sample was 4 min. Detection was performed in positive electrospray ionization mode, employing multiple reaction monitoring with transitions of 347.2→315.1 for nifedipine and 286.1→217.1 for letrozole (internal standard), respectively. Compared with the detection methods reported previously, the approach proposed in the current study is notably more simplified and easier to implement in practical operations. The standard curve of nifedipine illustrated good linearity over the concentration range of 1.114–222.8 ng mL −1 with a correlation coefficient greater than 0.9995. Additionally, both intra-day and inter-day accuracy and precision for nifedipine were well within the acceptable criteria. Subsequently, the fully validated method was applied to investigate the pharmacokinetic profiles of nifedipine in healthy Chinese volunteers.