Quantitation of seven low-dosage antipsychotic drugs in human postmortem blood using LC-MS-MS

In forensic toxicology, antipsychotic drugs are of considerable interest because of their abuse potential and their involvement in intoxications and suicides. In recent years, several new drugs dosed at low levels have entered the market and have put further demands on assays used. The aim of this work was to develop a validated liquid chromatography-tandem mass spectrometry assay for the quantitation of the low-dosage antipsychotic drugs buspirone, fluphenazine, flupenthixol, perphenazine, risperidone, ziprasidone, and zuclopenthixol in human postmortem blood. After liquid-liquid extraction using methyl t-butyl ether, compounds were separated on a Zorbax SB-CN column. Calibration curves were linear in the range 0.8-100 microg/L (r > 0.998) for all drugs. Both within- and between-day coefficients of variation were lower than 25% for all drugs at the LOQ, and extraction recoveries ranged between 58 and 112%. The possible presence of matrix effects was closely investigated. Fifty-four authentic samples were analyzed within the routine postmortem investigation, which resulted in the diagnosis of three fatal intoxications. Even though only a few intoxications were identified, the assay may present valuable information on suicidal deaths in psychotic patients where a true negative result implies noncompliance and a higher susceptibility for suicide. Without a sensitive enough method, this conclusion cannot be drawn. Therefore, we believe that antipsychotic drugs must be measured not only in toxic concentrations but also in therapeutic levels in postmortem cases.