Determination of antipsychotic drugs in nails and hair by liquid chromatography tandem mass spectrometry and evaluation of their incorporation into keratinized matrices

Abstract

Nail samples are an alternative to hair for long-term monitoring of drug use, although there are a limited number of studies about its applicability. This study presents the development and validation of a LC–MS/MS method for the determination of five antipsychotic drugs (clozapine, haloperidol, levomepromazine, olanzapine and quetiapine) in nail and in hair samples. Samples were washed with dichloromethane, pulverized with a ball mill, and incubated in water:acetonitrile (50:50 v/v) with horizontal agitation for 90 min. Then, samples were purified by solid phase extraction with OASIS MCX cartridges and analysed by LC–MS/MS. The analytical method was fully validated in nails and in hair, including: limits of detection (2.5 pg/mg and 2.5−10 pg/mg, respectively), limits of quantification (LOQ) (10 pg/mg and 10−20 pg/mg, respectively), linearity (LOQ to 10,000 pg/mg), selectivity (no endogenous or exogenous interferences), accuracy (97.4–106.9% and 97.3–108.2%, respectively), imprecision (<7.9% and <8.6%, respectively), extraction efficiency (62.3%–109.8% and 45.1%–83.6%, respectively), matrix effect (-35.6% to 654.4% and -71.0% to -10.8%, respectively) and autosampler stability after 72 h (%loss <12.4%). Moreover, paired fingernail, toenail and hair samples from 13 patients under chronic treatment were analysed, and concentrations in the different matrices were compared. Concentrations in real samples ranged from 11.3–8306 pg/mg in fingernails, from 12.7–1755.4 pg/mg in toenails and from 17.6–24045.4 pg/mg in hair. Hair concentrations were generally higher than nail concentrations; however, a variable pattern was found in fingernails and toenails depending on the case. In addition, concentrations in paired hair and nail samples from a patient under chronic treatment with quetiapine at different doses were studied for 1-year.