TY - JOUR
T1 - Determination of olanzapine in whole blood using simple protein precipitation and liquid chromatography-tandem mass spectrometry
AU - Nielsen, Marie Katrine Klose
AU - Johansen, Sys Stybe
N1 - Keywords: Antipsychotic Agents; Autopsy; Benzodiazepines; Calibration; Chromatography, Liquid; Forensic Toxicology; Humans; Precipitation; Reference Standards; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PY - 2009
Y1 - 2009
N2 - A simple, sensitive, and reproducible liquid chromatography-tandem mass spectrometry method has been developed and validated for the quantification of the antipsychotic drug olanzapine in whole blood using dibenzepine as internal standard (IS). After acidic methanol-induced protein precipitation of the whole blood samples, olanzapine and IS were chromatographed on a reversed-phase Zorbax Extend-C(18)-column at pH 9.0. Quantification was performed on a triple-quadrupole mass spectrometer employing electrospray ionization technique operating in multiple reaction monitoring and positive ion mode. Total chromatographic run time was 15 min, and calibration curve was linear over the concentration range of 0.005 to 0.50 mg/kg olanzapine in whole blood. The method was validated for selectivity, matrix interference, recovery, linearity, limit of detection, limit of quantitation (LOQ), accuracy, precision, and stability. The absolute recovery obtained was 103% for olanzapine and 68% for IS. An LOQ of 0.005 mg/kg olanzapine in whole blood was achieved. Inter- and intraday precision were less than 11% within concentrations from 0.01 to 0.50 mg/kg, and the accuracy ranged from 85 to 115%. The method was subsequently applied to 27 authentic samples, of which 20 were postmortem blood samples, from forensic investigations.
AB - A simple, sensitive, and reproducible liquid chromatography-tandem mass spectrometry method has been developed and validated for the quantification of the antipsychotic drug olanzapine in whole blood using dibenzepine as internal standard (IS). After acidic methanol-induced protein precipitation of the whole blood samples, olanzapine and IS were chromatographed on a reversed-phase Zorbax Extend-C(18)-column at pH 9.0. Quantification was performed on a triple-quadrupole mass spectrometer employing electrospray ionization technique operating in multiple reaction monitoring and positive ion mode. Total chromatographic run time was 15 min, and calibration curve was linear over the concentration range of 0.005 to 0.50 mg/kg olanzapine in whole blood. The method was validated for selectivity, matrix interference, recovery, linearity, limit of detection, limit of quantitation (LOQ), accuracy, precision, and stability. The absolute recovery obtained was 103% for olanzapine and 68% for IS. An LOQ of 0.005 mg/kg olanzapine in whole blood was achieved. Inter- and intraday precision were less than 11% within concentrations from 0.01 to 0.50 mg/kg, and the accuracy ranged from 85 to 115%. The method was subsequently applied to 27 authentic samples, of which 20 were postmortem blood samples, from forensic investigations.
M3 - Journal article
C2 - 19470224
SN - 0146-4760
VL - 33
SP - 212
EP - 217
JO - Journal of Analytical Toxicology
JF - Journal of Analytical Toxicology
IS - 4
ER -