Simultaneous determination of sutetinib and its active metabolite sutetinib N ‐oxide in human plasma by liquid chromatography–tandem mass spectrometry: Evaluation of plasma stability
| Autor: | Yuqiang Zhang, Sumin Cao, Xiaoyan Chen, Chongzhuang Tang, Ranran Li, Yanan Qiu |
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| Rok vydání: | 2020 |
| Předmět: |
Metabolite
Electrospray ionization Clinical Biochemistry Antineoplastic Agents Biochemistry Analytical Chemistry chemistry.chemical_compound Limit of Detection Tandem Mass Spectrometry Liquid chromatography–mass spectrometry Neoplasms Drug Discovery Humans Protein precipitation Protein Kinase Inhibitors Molecular Biology Active metabolite Pharmacology Chromatography Selected reaction monitoring Reproducibility of Results Oxides General Medicine Amides chemistry Linear Models Plasma stability Ammonium acetate Chromatography Liquid |
| Zdroj: | Biomedical Chromatography. 34 |
| ISSN: | 1099-0801 0269-3879 |
| DOI: | 10.1002/bmc.4918 |
| Popis: | From the point of view of drug efficacy and safety, pharmacokinetic profiles of both In this work, a sensitive and reliable liquid chromatographic-tandem mass spectrometric method was established for simultaneous determination of sutetinib and N-oxide metabolite (SNO) in human plasma and further applied to a pharmacokinetic study. Analytes were extracted from plasma samples (100 μl) via acetonitrile-induced protein precipitation and separated on a C18 column using ammonium acetate with ammonium hydroxide and acetonitrile as the mobile phase. Positive electrospray ionization was carried out through multiple reaction monitoring with transitions of m/z 440.2 → 367.1 and 446.2 → 367.1 for sutetinib and SNO, respectively. The method was linear within the concentration range of 0.5-100 ng/ml for both analytes. The precision, accuracy, selectivity, recovery and matrix effect of this method all met the requirements of bioanalytical guidance. In addition, a plasma stability assessment demonstrated unexpected results. Sutetinib was prone to form covalent conjugates with plasma albumin in vitro. The degree of covalent binding increased with increasing temperature, resulting in a significant decrease in its plasma concentrations. However, SNO could not easily bind with albumin owing to steric hindrance or electronegativity. Furthermore, sutetinib and SNO remained stable when blood and plasma samples were kept on wet ice. The validated method was successfully employed for the pharmacokinetic evaluation of sutetinib in patients with advanced malignant solid tumors. |
| Databáze: | OpenAIRE |
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