Determination of Chlorpromazine, Haloperidol, Levomepromazine, Olanzapine, Risperidone, and Sulpiride in Human Plasma by Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS).

BACKGROUND AND OBJECTIVE: In this study, turbo-ion spray as an interface of tandem mass spectrometry (MS/MS) was performed for sensitive and accurate quantification of chlorpromazine, haloperidol, levomepromazine, olanzapine, risperidone, and sulpiride in plasma samples. METHODS: Separation was performed by gradient reversed phase high-performance liquid chromatography using a mobile phase containing ammonium formiate 2 mM, pH 2.7, and acetonitrile flowing through a Restek PFP Propyl C18 analytical column (50 mm×2.1 mm i.d.) with particle size of 5 µm, at a flow rate of 800 µL/min. Positive ion fragments were detected in multiple reaction monitoring (MRM) mode. Sample preparation was achieved by solid phase extraction (SPE) (Oasis HLB). RESULTS: Mean extraction recoveries ranged from 82.75% to 100.96%. The standard calibration curves showed an excellent linearity, covering subtherapeutic, therapeutic, and toxic ranges. Intraday and interday validation using quality control (QC) samples were performed. The inaccuracy and imprecision were below 12% at all concentration levels. The limits of detection (LOD) and quantification (LOQ) for all analytes were under therapeutic ranges for all tested analytes. Thus, the proposed method was sensitive enough for the detection and determination of subtherapeutic levels of these antipsychotics in plasma samples. No interference of endogenous or exogenous molecules was observed and no carryover effects were recorded. CONCLUSION: According to the results, the proposed method is simple, specific, linear, accurate, and precise and can be applied for antipsychotic analysis in clinical routine. This method was applied for the determination of the tested antipsychotics in plasma samples taken from 71 individuals.

Antipsychotic-induced disorders: Reported cases and prospective study on muscle biomarkers after high exposure to haloperidol.

Antipsychotic drugs are known to induce neuromuscular effects. In this study, we review 13 years (2002-2014) of antipsychotic intoxications reported by the anti-poisoning center of Algiers (APCA). The most recorded symptoms were neuromuscular/muscular disorders, of which haloperidol was the most inducer among all antipsychotics. A prospective study was conducted between December 2012 and January 2017 to evaluate muscle effects generated after intentional or accidental ingestion of haloperidol. Fifty-one patients admitted in different emergency departments in Algiers were included in this study. Urine and blood samples were collected from each patient for biological and toxicological monitoring and a group of healthy volunteers was assessed for comparison purpose. There was no significant difference in plasma lactate dehydrogenase (LDH) activity between healthy volunteers and exposed patients even when high levels of haloperidol were recorded. In contrast, selenium concentration and creatine kinase (CK) activity in plasma samples were significantly higher in patients exposed to high levels of haloperidol compared to healthy volunteers. Large percentage of patients exposed to high levels of haloperidol presented a significant elevated CK activity and high selenium concentration regarding the physiological thresholds. Additionally, CK activity and selenium concentration correlated positively with plasma content of haloperidol suggesting a dose-dependent relationship. In conclusion, some biomarkers (CK and selenium) may reflect muscle adverse effects of high haloperidol exposure that result possibly from muscle rigidity.