Simultaneous quantitation of quetiapine and its active metabolite norquetiapine in rat plasma and brain tissue by high performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC-MS/MS)

• Development of HPLC tandem mass spectrometry method.
• Optimization of extraction process for multiple analytes.
• Validation of method.
• Application of method in rat model.

A sensitive method to simultaneously quantitate quetiapine and norquetiapine in rat plasma and brain tissue was developed using a one-step liquid–liquid extraction for sample preparation and LC-MS/MS for detection. The method provided a linear range of 1.0–500.0 ng/mL for each analyte in plasma and 3.0–1500.0 ng/g in brain tissue. The method was validated with precision within 15% relative standard deviation (RSD), accuracy within 15% relative error (RE), matrix effects within 10% and a consistent recovery. This method has been successfully applied in a preclinical study of quetiapine and norquetiapine to simultaneously determine their concentrations in rat plasma and brain tissue.