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UPLC–MS–MS Analysis of Quetiapine and Its Two Active Metabolites, 7-Hydroxyquetiapine and 7-Hydroxy-N-dealkylquetiapine, in Rat Plasma and Cerebrospinal Fluid

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Abstract

Quetiapine (QP) is an antipsychotic agent widely used to treat a variety of human psychotic disorders. 7-Hydroxyquetiapine (QPOH) and 7-hydroxy-N-dealkylquetiapine (QPND) are its two active metabolites. A rapid and sensitive ultra-performance liquid chromatographic–tandem mass spectrometric method has been developed for analysis of the three agents in plasma and cerebrospinal fluid (CSF) from rats. The assay was based on liquid–liquid extraction of 100-μL samples. The methods were validated for QP, QPOH, and QPND in both types of sample. Limits of detection (LOD) in plasma were 0.02, 0.01, and 0.02 ng mL−1 for QP, QPOH, and QPND, respectively; in CSF samples the respective values were 0.02, 0.01, and 0.01 ng mL−1. The utility of the method was demonstrated by analysis of the pharmacokinetics and CSF distribution properties of QP and its two active metabolites in the plasma and CSF in rats.

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Acknowledgments

We gratefully acknowledge AstraZeneca Pharmaceutical (London, UK) for providing us with pure compounds.

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Authors and Affiliations

  1. Clinical Pharmacy and Pharmacology Institute, Second Xiang Ya Hospital, Central South University, 410011, Changsha, China

    Ji-Ying Tu, Ping Xu, Dan-Hua Xu & Huan-De Li

  2. School of Pharmaceutical Sciences, Central South University, 410013, Changsha, China

    Ji-Ying Tu, Dan-Hua Xu & Huan-De Li

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  1. Ji-Ying Tu
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  2. Ping Xu
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  3. Dan-Hua Xu
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  4. Huan-De Li
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Correspondence to Huan-De Li.

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Tu, JY., Xu, P., Xu, DH. et al. UPLC–MS–MS Analysis of Quetiapine and Its Two Active Metabolites, 7-Hydroxyquetiapine and 7-Hydroxy-N-dealkylquetiapine, in Rat Plasma and Cerebrospinal Fluid. Chroma 68, 525–532 (2008). https://doi.org/10.1365/s10337-008-0770-8

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  • DOI: https://doi.org/10.1365/s10337-008-0770-8

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