Monocrotaline (MCT) is a pyrrolizidine alkaloid that can induce hepatic sinusoidal damage, pulmonary hypertension, renal toxicity, and heart disease. Monocrotaline N-oxide (MNO), the primary metabolite of MCT, is less toxic; however, it can convert back to MCT to exhibit its toxicity. This study developed and validated a rapid and sensitive LC–MS/MS method for the simultaneous determination of MCT and monocrotaline N-oxide in rat plasma. The method has a linearity over the concentration range of 1–2000 ng/mL with correlation coefficients (r) >0.997 for each analyte. The results of selectivity, matrix effect, accuracy and precision, and recovery were all within the acceptance criteria. The validated method has been successfully applied to study pharmacokinetic behaviors and bioavailability of MCT in rats. MCT was rapidly absorbed (T_max: 0.400 ± 0.149 h) after oral administration, and the absolute bioavailability of MCT was 78.2%.

中文翻译：

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使用 LC-MS/MS 同时测定大鼠血浆中野百合碱及其 N-氧化物代谢物：在药代动力学研究中的应用

野百合碱 (MCT) 是一种吡咯里西啶生物碱，可引起肝窦损伤、肺动脉高压、肾毒性和心脏病。MCT 的主要代谢物野百合碱 N-氧化物 (MNO) 毒性较小；但是，它可以转化回 MCT 以显示其毒性。本研究开发并验证了一种快速灵敏的 LC-MS/MS 方法，用于同时测定大鼠血浆中 MCT 和野百合碱 N-氧化物。该方法在 1–2000 ng/mL 的浓度范围内具有线性关系，相关系数为 ( r) >0.997，每种分析物。选择性、基质效应、准确度和精密度以及回收率的结果均在可接受标准内。该验证方法已成功应用于研究大鼠 MCT 的药代动力学行为和生物利用度。_MCT口服后吸收迅速（Tmax：0.400±0.149 h），MCT绝对生物利用度为78.2%。