High-performance liquid chromatographic determination of the polar metabolites of nifedipine in plasma, blood and urine

Rapid and simultaneous determination of nifedipine and dehydronifedipine in human plasma by liquid chromatography–tandem mass spectrometry: Application to a clinical herb–drug interaction study

“…Although the sensitivity of GC/MS is high in pharmacokinetic and pharmacogenetic studies, the GC method has several concerning drawbacks, such as thermal degradation of NIF and DNIF due to high temperatures during analysis. Among the LC procedures reported, most of them are the combination of LC separation with UV detection [3,18,[23][24][25][35][36][37][38][39], electrochemical detection [18,[40][41][42][43], or less frequently, with MS detection [19]. In these reported LC methods, only five of which are able to simultaneously quantitate NIF and DNIF in biological fluids [19,30,35,38,39].…”

“…Among the LC procedures reported, most of them are the combination of LC separation with UV detection [3,18,[23][24][25][35][36][37][38][39], electrochemical detection [18,[40][41][42][43], or less frequently, with MS detection [19]. In these reported LC methods, only five of which are able to simultaneously quantitate NIF and DNIF in biological fluids [19,30,35,38,39]. However, these analytical methods without coupling with MS detection all have a lower limit of quantification (LLOQ) of above 50 ng/mL [30,35,38,39], while the LC/MS method reported by Streel et al [19] gives a significantly improved LLOQ (0.5 ng/mL) for both NIF and DNIF.…”

Method Development Challenges and Regulatory Expectation in Nifedipine

“…Roosmemalen et al [22] Streel et al [25] Wang et al [26] Wang et al [27] Patel et al [28] Plasma volume (ml) …”

“…The ex vivo inter-conversion of nifedipine and its metabolites are challenging in terms of bioanalysis. Although Roosmemalen et al reported a method on estimation of polar metabolites of nifedipine, arresting ex vivo inter-conversion among metabolites and analyte [22] remained unaddressed. Reported LC-MS/MS methods showed marked limitations as these methods are not tuned to labile metabolite separation and arresting ex vivo degradation of nifedipine [25][26][27][28].…”

“…These methods include HPLC [8][9][10][11][12][13][14] coupled with UV detectors or electrochemical detector, but tedious sample processing technique, lengthy analysis time and lack of sensitivity were major limitations in these methods. Diverse detection techniques like electron-capture detection [15][16][17][18][19][20], nitrogen phosphorus detection [21] and mass spectrometric (MS) detection [22,23] were reported. However, scope of thermal decomposition of nifedipine under gas chromatography conditions was a co ncern and MS methods are usually preferred.…”