A More Rapid, Sensitive, and Specific HPLC-MS/MS Method for Nifedipine Analysis in Human Plasma and Application to a Pharmacokinetic Study

Abstract

A more rapid, sensitive and specific high-performance liquid chromatography coupled to ?tandem mass spectrometry (HPLC-MS/MS) was developed and validated for the quantification of nifedipine in human plasma, and applied to the pharmacokinetic study of nifedipine in Chinese healthy volunteers. Nifedipine and internal standard (IS) acetaminophen in plasma were extracted with ethyl acetate, separated on a C18 (150?mm?4.6?mm, 5??m) reversed-phase column, eluted with acetonitrile mixed with 5?mM ammonium acetate solution (pH=6.62) (60:40, v/v), ionized by negative ion pneumatically assisted electrospray and detected in the multi-reaction monitoring mode using precursor?product ions of m/z 354.1?222.2 for nifedipine and 150.1?107.1 for the IS. A single oral dose of 20?mg nifedipine sustained release tablets and blood samples (4?mL) was collected before and 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, and 36?h after administration. The main pharmacokinetic parameters of nifedipine, as Tmax, t1/2?, t1/2?, t1/2z, Cmax, AUC0~36, AUC0~? were 2.80?0.50?h, 6.78?2.52?h, 6.82?2.53?h, 6.69?2.22?h, 76.69?19.51 (ng/mL), 546.49?162.28 (ng???h/mL) and 564.05?176.74 (ng???h/mL), respectively. The calibration curve was linear over the concentration range of 0.17?102?ng/mL (r2>0.99, n=5) with a lower limit of quantification (LLOQ) of 0.17?ng/mL. The intra- and inter-day precision was less than 15% for all quality control samples at concentrations of 0.42, 6.53 and 81.60?ng/mL and the accuracy (relative error, RE) was ???3.92% to 7.31% at 3 quality control levels. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision and stabilities were validated, and can fulfill the requirement of pharmacokinetic study of nifedipine sustained release tablets in Chinese volunteers.

eNOS-Dependent Antisenscence Effect of a Calcium Channel Blocker in Human Endothelial Cells

“…Importantly, most of these studies have revealed that calcium channel blockers at the doses used did not affect blood pressure. The concentration of nifedipine used in our present study (1 nM) is in the range of clinically relevant concentrations found in plasma of patients treated with this drug [31] – [33] . It should be noted, however, that the concentrations above and below 1 nM were found to have a limited effect on endothelial cell senescence.…”

UV‐Light Photoelectrochemical Sensor Based on the Copper Tetraamino‐Phthalocyanine‐modified ITO Electrode for the Detection of Nifedipine in Drugs and Human Serum

“…Excessive use of NP can trigger hypotension and proarrhythmic effects. Although HPLC and other combination technologies [12][13][14] have high sensitivity and selectivity, these analytical methods involve costly and time-consuming processes. Modern instrumental analysis techniques such as high-performance liquid chromatography (HPLC), 5,6 gas chromatography, 7,8 capillary gas chromatography, 9 and spectrophotometry 10,11 were established and applied to the determination of NP.…”

“…Modern instrumental analysis techniques such as high‐performance liquid chromatography (HPLC), gas chromatography, capillary gas chromatography, and spectrophotometry were established and applied to the determination of NP. Although HPLC and other combination technologies have high sensitivity and selectivity, these analytical methods involve costly and time‐consuming processes. It is urgently necessary to develop a method with simple operation, fast response, and low cost for use in NP detection.…”

Pharmacokinetic and Tolerability Comparison of Sustained and Immediate Release Oral Formulations of Nifedipine Tablet Formulations: A Single-Dose, Randomized, Open-Label, Two-Period, Two-Way Crossover Study in Healthy, Fasting Egyptian Male Volunteers

“…Nifedipine concentrations in plasma samples were analyzed using validated high performance liquid chromatography (HPLC) method with UV absorbance detection at 240 nm [14][15][16]. The analysis was performed in HPLC system equipped with a variable-wavelength ultraviolet (UV) detector and an automatic injector (LC-10 VP, Shimadzu Scientific Instrument, Kyoto, Japan).…”