The development and validation of a method for quantifying olanzapine in human plasma by liquid chromatography tandem mass spectrometry and its application in a pharmacokinetic study.

1. A rapid method using liquid chromatography tandem mass spectrometry for the quantification of olanzapine (OLZ) in human plasma was developed and validated. Venlafaxine was used as the internal standard (IS), and the samples were extracted from 400-μL human plasma with methyl tert-butyl ether for liquid-liquid extraction. 2. Chromatography was performed using an ACE C18, 125 × 4.6-mm i.d., 5-μm column. The mobile phase consisted of water with 0.1% formic acid for solvent A and acetonitrile with 0.1% formic acid for solvent B (50 : 50 v/v) in isocratic mode. The flow rate was 1.2 mL/min. The retention times for OLZ and the IS were 0.78 and 1.04 min, respectively. Tandem mass spectrometry operating in positive electrospray ionization mode with multiple reaction monitoring was used to detect OLZ and the IS (m/z: 313.1 > 256.1 and 278.1 > 260.2, respectively). 3. No significant matrix effects were observed on OLZ and the IS retention times, and the mean recovery of OLZ was 90.08%. The assay was linear in the concentration range of 1-20 ng/mL (R(2) = 0.9976). The intra- and inter-day precision were < 11.60% and the accuracy was < 1.66%. 4. This validated method was successfully applied to a pharmacokinetic study in which 10-mg OLZ tablets were administered to healthy volunteers and their plasma OLZ levels were monitored over time. The tests showed that the OLZ test and reference drug (Zyprexa(®)) were bioequivalent, as 90% of the confidence intervals were within the 80-125% interval proposed by regulatory agencies.

RCT Entities:   Population Interventions Outcomes