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

Abstract

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.

Dried Blood Spot Technique-Based Liquid Chromatography-Tandem Mass Spectrometry Method as a Simple Alternative for Benznidazole Pharmacokinetic Assessment

“…The mass spectrometer was set up to obtain the maximum signal without fragmentation in the ionization source and an MRM with the most sensitive and stable fragment to obtain a high signal/noise ratio ( 24 ). The chromatographic parameters were optimized to obtain separation (resolution, >1.5) between the analyte and IS with a good shape peak (tailing factor, <1.2), good run time (<5.0), and minimum matrix effect associated with the sample preparation technique.…”

Pharmaceutical studies on and clinical application of olanzapine suppositories prepared as a hospital preparation

“…We were unable to employ HPLC with ultraviolet. Liquid chromatography tandem mass spectrometry (LC-MS/MS) is needed in order to measure olanzapine blood concentrations [ 26 ]. Another reason is the lower frequency of blood sampling in terminally ill patients with cancer.…”

A Review of Advances in Bioanalytical Methods for the Detection and Quantification of Olanzapine and Its Metabolites in Complex Biological Matrices

“…To extract the analyte quantitatively, the solvent chosen should not only dissolve olanzapine completely but also be able to break the association with proteins. In the methodology of preparing samples containing olanzapine, the following were used: ethyl acetate [ 32 , 47 ], diethyl ether [ 43 ], isopropyl ether [ 48 ], and tert-butyl methyl ether (MTBE) [ 19 , 33 , 40 , 41 , 49 , 51 , 52 ]. Mixtures of organic solvents were also used, the extraction properties of which may be better than for each solvent alone: hexane/MTBE [ 39 ], hexane/dichloromethane [ 44 ], hexane/isoamyl alcohol [ 37 ], heptane/isoamyl alcohol [ 36 , 42 ], diethyl ether/diisopropyl ether [ 53 ], diethyl ether/dichloromethane [ 34 , 54 ], butyl acetate/butanol [ 50 ], butanol/cyclohexane [ 45 ], and dichloromethane/cyclohexane [ 46 ].…”