Comparison of time-of-flight mass spectrometry to triple quadrupole tandem mass spectrometry for quantitative bioanalysis: Application to antipsychotics

Tandem mass spectrometry (MS/MS) is frequently used for the detection of small molecules in biological samples because of the high specificity and sensitivity associated with these instruments. Time-of-flight mass spectrometers (TOF-MS) are typically used qualitatively for accurate mass determination; however, recently they have gained more attention for quantitation. A selective and sensitive TOF-MS method was validated to determine risperidone, its active metabolite paliperidol, haloperidol, clozapine, and olanzapine in rat plasma using midazolam as an internal standard (IS). Comparisons were made between the use of LC-TOF and LC-MS/MS using a triple quadrupole for these compounds for specificity, linearity, precision, accuracy, matrix effects, and recovery. A focus of this study was the evaluation of recent instrumental and software improvements, which have been made to time-of-flight mass analyzers to increase the linearity and quantitative capabilities of these instruments.