Determination of cilnidipine, a new calcium antagonist, in human plasma using high performance liquid chromatography with tandem mass spectrometric detection.
A rapid, sensitive and reliable high performance liquid chromatographic method coupled with tandem mass spectrometry (HPLC-MS/MS) has been developed and validated for the determination of cilnidipine, a relatively new calcium antagonist, in human plasma. The reversed-phase chromatographic system was interfaced with a TurboIonSpray (TIS) source. Nimodipine was employed as the internal standard (IS). Sample extracts following protein precipitation were injected into the HPLC-MS/MS system. The analyte and IS were eluted isocratically on a C18 column, with a mobile phase consisting of CH(3)OH and NH(4)Ac (96:4, v/v). The ions were detected by a triple quadrupole mass spectrometric detector in the negative mode. Quantification was performed using multiple reaction monitoring (MRM) of the transitions m/z 491.2-->122.1 and m/z 417.1-->122.1 for cilnidipine and for the IS, respectively. The analysis time for each run was 3.0 min. The calibration curve fitted well over the concentration range of 0.1-10 ngmL(-1), with the regression equation Y=(0.103+/-0.002)X+(0.014+/-0.003) (n=5), r=0.9994. The intra-day and inter-day R.S.D.% were less than 12.51% at all concentration levels within the calibration range. The recoveries were between 92.71% and 97.64%. The long-term stability and freeze-thaw stability were satisfying at each level. The present method provides a modern, rapid and robust tool for pharmacokinetic studies of cilnidipine.
Zhang
Xianhua
X
Peking University Third Hospital, Peking University TDMCT Center, Beijing 100083, PR China.
Zhai
Suodi
S
Zhao
Rongsheng
R
Ouyang
Jin
J
Li
Xiaoguang
X
Baeyens
Willy R G
WR
D000328:Adult; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004095:Dihydropyridines / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013696:Temperature
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C065927:cilnidipine; D002118:Calcium