Quantification of a cytochrome P450 3A4 substrate, buspirone, in human plasma by liquid chromatography-tandem mass spectrometry.
ABSTRACT A sensitive HPLC-tandem mass spectrometry method was developed for determination of buspirone levels in human plasma. After solid phase extraction and reversed phase HPLC separation, detection of buspirone and the internal standard (prazosin) was performed using eletrospray ionization and selected reaction monitoring in the positive ion mode. Linear calibration curves were established over a concentration range of 0.025-2.5 ng/ml when 0.5 ml aliquots of plasma were used. Satisfactory results of within-day precision (RSD of 1.9-7.7%) and accuracy (% difference of 0.5-6.6%) and between-day precision (RSD of 3.7-11.1%) and accuracy (% difference of 2.2-6.8%) were obtained. The assay has been successfully applied to the analysis of buspirone levels in more than 500 human plasma samples collected from a drug interaction study.
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ABSTRACT: Antipsychotic drugs (APs) are prescribed for a wide range of psychotic illnesses. With more than 35 APs currently available worldwide, this drug class has rapidly gained importance in both clinical and forensic settings. On account of their chemical properties, many APs are present in human specimens at very low concentrations, which complicate their detection using standard gas chromatography-mass spectrometry (GC-MS) procedures that often cannot provide the required sensitivity. Recent advances in liquid chromatography-(tandem) mass spectrometry LC-MS(/MS) technology have enabled accurate detection and quantification of these compounds in various human specimens, indicated by the increasing number of published methods. Method validation has been a particular focus of analytical chemistry in recent times. Recommendations set by several guidance documents are now widely accepted by the toxicology community, as reflected by the guidelines drafted by leading toxicological societies. This review provides a critical review of single-stage and tandem LC-MS procedures for the detection and quantification of APs, with a particular emphasis on appropriate method validation. The quality of published methods is inconsistent throughout the literature. While the majority of authors incorporate some validation experiments in their respective method development, a large number of published methods lack essential components of method validation, which are considered mandatory according to the guidelines. If adapting a method for the detection of APs for use in a laboratory, analysts should ensure successful validation experiments for appropriateness and completeness have been conducted, and perform additional experiments when indicated.Drug Testing and Analysis 05/2012; 4(6):376-94. · 2.54 Impact Factor