Abstract
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.
Highlights
Antipsychotics, named neuroleptics, are widely used to treat several mental disorders
The extraction efficiency was evaluated by comparing detector signals obtained from extracts of quality control (QC) samples at low, medium, and high levels of all tested antipsychotics with those obtained with the corresponding standard solutions added to extracted matrices (Table 3)
The mean recoveries were more than 80% showing the higher efficiency of the proposed solid phase extraction (SPE) procedure for some analytes compared to those obtained with other methods in previous studies (Table 6)
Summary
Antipsychotics, named neuroleptics, are widely used to treat several mental disorders. As defined by the “The AGNP-TDM Expert Group Consensus Guidelines: Therapeutic Drug Monitoring in Psychiatry”, therapeutic ranges are narrow and low plasma concentrations are often seen with antipsychotics. Sensitive and specific analytical methods are required for their reliable, accurate, and precise quantification [3]. The proposed method was sensitive enough for the detection and determination of subtherapeutic levels of these antipsychotics in plasma samples. 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
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