Simultaneous determination of a novel M3 muscarinic receptor antagonist and its active 5-OH metabolite in human plasma using liquid chromatography/tandem mass spectrometry
| Autor: | Man-Wai Lo, Hengchang Song, Kerri X Yan, Kerry Riffel |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Receptor
Muscarinic M3 Chromatography Chemistry Metabolite Coefficient of variation Clinical Biochemistry Pharmaceutical Science Muscarinic Antagonists Mass spectrometry High-performance liquid chromatography Receptors Muscarinic Mass Spectrometry Analytical Chemistry Matrix (chemical analysis) Standard curve chemistry.chemical_compound Liquid chromatography–mass spectrometry Drug Discovery Humans Quantitative analysis (chemistry) Spectroscopy Chromatography Liquid |
| Zdroj: | Journal of pharmaceutical and biomedical analysis. 27(5) |
| ISSN: | 0731-7085 |
| Popis: | A sensitive, specific, and robust liquid chromatography (LC)/mass spectrometry (MS)/MS method has been developed and validated for a novel M3 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 ≤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. |
| Databáze: | OpenAIRE |
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