Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Jul 15;1242:124209. doi: 10.1016/j.jchromb.2024.124209. Epub 2024 Jun 14.
Decitabine is a DNA methyltransferase inhibitor used in the treatment of acute myeloid leukemia and myelodysplastic syndrome. The notion that ongoing trials are presently exploring the combined use of decitabine, with or without the cytidine deaminase inhibitor cedazuridine, and other antileukemic drugs necessitates a comprehensive understanding of pharmacokinetic properties and an evaluation of drug-drug interaction liabilities. We report here the development and validation of a sensitive UHPLC-MS/MS method for quantifying decitabine in mouse plasma, which should be useful for such studies. The method involved a one-step protein precipitation extraction, and chromatographic separation on an XBridge HILIC column using gradient elution. The method was found to be robust, accurate, precise, and sufficiently sensitive (lower limit of quantitation, 0.4 ng/mL) to determine decitabine concentrations in microvolumes of plasma from mice receiving the agent orally or intravenously in the presence or absence of cedazuridine.
地西他滨是一种 DNA 甲基转移酶抑制剂，用于治疗急性髓系白血病和骨髓增生异常综合征。目前正在进行的临床试验正在探索地西他滨联合或不联合胞苷脱氨酶抑制剂西他滨嘧啶以及其他抗白血病药物的联合应用，这需要全面了解药代动力学特性并评估药物相互作用的风险。我们在此报告了一种灵敏的 UHPLC-MS/MS 方法的开发和验证，用于定量检测小鼠血浆中的地西他滨，这对于此类研究将非常有用。该方法涉及一步蛋白沉淀提取，在 XBridge HILIC 柱上进行梯度洗脱的色谱分离。该方法具有稳健性、准确性、精密度，并且足够灵敏（定量下限为 0.4ng/mL），可用于检测经口或静脉给予地西他滨的小鼠在存在或不存在西他滨嘧啶时的微体积血浆中的地西他滨浓度。
