Determination of nimodipine in human plasma by ultra performance liquid chromatography-tandem mass spectrometry and pharmacokinetic application

A fast and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination and pharmacokinetic study of nimodipine in human plasma. With nitrendipine as the internal standard, sample pretreatment involved one-step extraction with diethyl ether of 0.5 ml plasma. The separation was carried out on an ACQUITY UPLC (TM) BEH C-18 column (50 mm x 2.1 mm, i.d., 1.7 mu m) with water and acetonitrile (both containing 0.1 % formic acid) as the mobile phase under gradient conditions at a flow rate of 0.35 ml/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. The standard curves were linear (r(2) >= 0.99) over the concentration range of 0.20-100 ng/ml with a limit of quantification (LLOQ) of 0.20 ng/ml. The intra- and inter-day precision (R.S.D.) values were below 14% and the accuracy (relative error R.E.) was ranged from -2.2% to 7.7% at all three quality control (QC) levels. The method herein described was superior to previous methods and successfully applied to the pharmacokinetic study of nimodipine tablets in healthy male volunteers after oral administration. (c) 2007 Elsevier B.V. All rights reserved.