Time resolved analysis of risperidone and 9-hydroxy-risperidone in hair using LC/MS-MS

Area of Science:

• Forensic Toxicology
• Pharmacokinetics
• Analytical Chemistry

Background:

• Risperidone (RSP) is a crucial second-generation antipsychotic for schizophrenia and anxiety.
• Hair analysis offers a wide surveillance window for drug monitoring.
• Quantifying RSP and its metabolite in hair is vital for treatment adherence and pharmacokinetic studies.

Purpose of the Study:

• To develop and validate a simple, fast method for detecting and quantifying risperidone (RSP) and 9-hydroxy-risperidone (9-OH-RSP) in human hair.
• To apply the validated method to analyze hair samples from psychiatric patients undergoing RSP treatment.
• To investigate the relationship between administered dose and drug concentration in hair for both RSP and its metabolite.

Main Methods:

• Hair sample preparation involved washing, pulverization, ultrasound-assisted incubation, and liquid/liquid extraction.
• Quantification was performed using Liquid Chromatography-Tandem Mass Spectrometry (LC/MS-MS) in selected reaction monitoring mode.
• Methaqualone was used as the internal standard for accurate quantification.

Main Results:

• The validated method demonstrated high precision (CV <15%), accuracy, and sensitivity (LOD as low as 0.90 pg/mg for RSP).
• RSP concentrations in patient hair ranged from 36 to 4765 pg/mg, and 9-OH-RSP from 14 to 57 pg/mg.
• Preliminary data indicated a stronger correlation between administered dose and hair concentration for 9-OH-RSP compared to RSP.

Conclusions:

• A robust LC/MS-MS method for RSP and 9-OH-RSP in hair was successfully developed and validated.
• The method enables the quantification of antipsychotic drug levels in psychiatric patients' hair.
• 9-OH-RSP may serve as a more reliable biomarker than RSP for assessing long-term drug exposure and adherence in hair analysis.