Validated LC-MS-MS method for determination of m-nisoldipine polymorphs in rat plasma and its application to pharmacokinetic studies.
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 microm) 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 TurboIonSpray ionization (ESI) source. The method was sensitive with a lower limit of quantification (LLOQ) of 0.2 ng/mL, with good linearity (r>or=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.
Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, PR China.
Hairong
H
Wang
Lantong
L
Zhang
Qiao
Q
Wang
Zhifang
Z
Yuan
Min
M
Li
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D015737:Nisoldipine / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D015737:Nisoldipine