Determination of seven selected antipsychotic drugs in human plasma using microextraction in packed sorbent and gas chromatography–tandem mass spectrometry

Abstract

A method using microextraction by packed sorbent (MEPS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) is described for the determination of seven antipsychotic drugs in human plasma. The studied compounds were chlorpromazine (CPZ), haloperidol (HAL), cyamemazine, quetiapine, clozapine, olanzapine (OLZ), and levomepromazine; promazine, protriptyline, and deuterated CPZ were used as internal standards. The validation parameters included selectivity, linearity and limits of detection and quantitation, intra- and interday precision and trueness, recovery, and stability and were studied according to internationally accepted guidelines. The method was found to be linear between the lower limit of quantitation and 1000 ng/mL, except for OLZ and HAL (200 ng/mL), with determination coefficients higher than 0.99 for all analytes, and extraction efficiencies ranged from 62 to 92 %. Intra- and interday precision ranged from 0.24 to 10.67 %, while trueness was within a ±15 % interval from the nominal concentration for all analytes at all studied levels. MEPS has shown to be a rapid procedure for the determination of the selected antipsychotic drugs in human plasma, allowing reducing the handling time and the costs of analysis. Furthermore, GC-MS/MS has demonstrated to be a powerful tool for the simultaneous quantitation of the studied compounds, enabling obtaining adequate selectivity and sensitivity using a sample volume of as low as 0.25 mL.

A validated GC/MS method for the investigation of quetiapine-related deaths in Greece

“…Several methods have been already published for the determination of quetiapine in biological samples using LC [37][38][39][40][41] or GC methods [6,18,21,32,33,42,43]. The aim of this work was to investigate quetiapine-related lethal cases to assess the contribution of quetiapine to the cause of death.…”

“…During the last decades, several quetiapine-related postmortem cases have been recorded in Europe [18,34,43,49], Australia [14], Canada [6] and the United States [21,25,32,33]. In 2011, FDA requested from the manufacturer company, AstraZeneca, to add "a new heart warning" to the information label of the quetiapine pharmaceutical formulations.…”

Avaliação da microextração líquido-líquido dispersiva para determinação do levetiracetam e da risperidona por técnicas cromatográficas acopladas a espectrometria de massas

“…A esquizofrenia é uma das mais complexas desordens psiquiátricas que afetam 1,5 % da população mundial (FONSECA et al, 2013 mulher é de 2:1, porém acima dos 50 anos, esta proporção inverte (CHAVES, 2000).…”

“…A risperidona (RSP, figura 2.1a) é um dos fármacos antipsicóticos mais prescritos no mundo (MANDRIOLI et al, 2011), sendo indicada principalmente para o tratamento da esquizofrenia (FONSECA et al, 2013). Também foi aprovada para o tratamento das desordens maníaco-depressivas, crises bipolares com presença de sintomas psicóticos e para desordens obsessivo-compulsivas quando associada a um fármaco seletivo na inibição da receptação serotoninérgica (MANDRIOLI et al, 2011).…”

“…A RSP compõe a classe dos antipsicóticos atípicos, e diferentemente dos típicos, ou de primeira geração, seu mecanismo de ação age antagonizando seletivamente os receptores dopaminérgicos tipo D2, D3 e D4 e os receptores serotoninérgicos do tipo 5-HT2a e 5-HT7 (FONSECA et al, 2013;MAURI et al, 2007).…”