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Simultaneous determination of a novel M3 muscarinic receptor antagonist and its active 5-OH metabolite in human plasma using liquid chromatography/tandem mass spectrometry by Kerri X Yan; Hengchang Song; Kerry Riffel; Man-Wai Lo is a Chemistry article available to read on EtoBox.

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A sensitive, specific, and robust liquid chromatography (LC)/mass spectrometry (MS)/MS method has been developed and validated for a novel M 3 muscarinic receptor antagonist (I) and its active 5-OH metabolite (II) in human plasma. The assay involves a two-step liquid-liquid extraction of the compounds from human plasma, high performance liquid chromatography (HPLC) separation, and MS/MS for the detection of the analytes. The method provides a linear response from a quantitation limit of 0.05-20 ng/ml for I and 0.1-20 ng/ml for II using 1 ml of plasma. The mean absolute recovery was 85.4% for I and 80.8% for II, respectively. The intra-assay accuracy of I and II averaged from 95.0 to 105.3% with coefficient of variation (CV) values 5 6.5% over the standard curve range. The stability study showed that I and II are stable in the plasma matrix over a period of 11 months at -70 °C. The accuracy, ruggedness, and reproducibility of this method were demonstrated by analyzing over 5000 plasma samples in clinical pharmacokinetics studies over a 6-month period.

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Author

Kerri X Yan; Hengchang Song; Kerry Riffel; Man-Wai Lo

Publisher

Elsevier Science; Elsevier ; Elsevier BV (ISSN 0731-7085)

Published

2002

Language

EN

Field

Chemistry (Physical Sciences)