Validated LC-MS-MS method for determination of m-nisoldipine polymorphs in rat plasma and its application to pharmacokinetic studies

摘要

A sensitive and specific liquid chromatography-tandem mass spectrometric (LC-MS-MS) method has been developed to determine m-nisoldipine in rat plasma. Sample was pretreated by a single-step protein precipitation with acetonitrile, in contrast to the liquid-liquid procedure frequently used for the extraction of 1,4-dihydropyridines from biologic samples. Separation of analyte and internal standard (I.S.) was performed on a Symmetry RP-C 18 analytic column (50 mm x 4.6 mm, 3.5 mu m) with a mobile phase consisting of acetonitrile-water (80:20. v/v) at a flow rate of 0.5 ml/min. The API 4000 triple quadrupole mass spectrometer was operated in multiple reaction monitoring (MRM) scan mode using TurbolonSpray ionization (ESI) source. The method was sensitive with a lower limit of quantification (LLOQ) of 0.2 ng/mL, with good linearity (r >= 0.9982) over the linear range of 0.2-20 ng/mL. All the validation data, such as accuracy, precision, and inter-day repeatability, were within the required limits. The method was successfully applied to pharmacokinetic and relative bioavailability studies of m-nisoldipine polymorphs in rats. (c) 2006 Elsevier B.V. All rights reserved.