Yang Wenqian, Yang Zimeng, Liu Jieru, Liu Dan, Wang Yongjun
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Asian J Pharm Sci. 2019 Nov;14(6):687-697. doi: 10.1016/j.ajps.2018.08.003. Epub 2018 Sep 11.
In 2015, liposomal formulation of irinotecan (ONIVYDE) has been approved by FDA and widely applied in the treatment of pancreatic cancer. ONIVYDE is a novel liposome formulation, entrapping CPT-11 in the aqueous core of vesicles using a modified gradient loading method. Due to toxicity concerns, it is essential to explore a rapid and reliable method to effectively isolate and quantify the non-liposomal, namely, free CPT-11and total CPT-11 in plasma. This study focuses on separation of non-liposomal CPT-11, evaluation of the pharmacokinetics of free CPT-11 and total CPT-11 and bio-distribution after intravenous administration of CPT-11 liposome. Free CPT-11 in plasma was separated by solid-phase extraction (SPE). The amount of total CPT-11 and main metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) in plasma was quantified by ultra-performance liquid chromatography-MS/MS. The calibration curves fitted well and lower limit of quantitation for SN-38, free CPT-11, total CPT-11 and CPT-11 in tissue and were 5 ng/ml, 10 ng/ml, 4.44 ng/ml and 25 ng/ml respectively. The recoveries, precision and accuracy of the method appear satisfactory. Using this method, the pharmacokinetics and bio-distribution of CPT-11 liposome formulation after an intravenous dose of 2.5 mg/kg were then investigated.
2015年，伊立替康脂质体制剂（ONIVYDE）已获美国食品药品监督管理局（FDA）批准，并广泛应用于胰腺癌治疗。ONIVYDE是一种新型脂质体制剂，采用改良梯度载入法将CPT - 11包裹于囊泡的水相核心中。鉴于毒性问题，探索一种快速可靠的方法以有效分离和定量血浆中的非脂质体形式，即游离CPT - 11和总CPT - 11至关重要。本研究聚焦于非脂质体CPT - 11的分离、游离CPT - 11和总CPT - 11的药代动力学评估以及CPT - 11脂质体静脉给药后的生物分布。血浆中的游离CPT - 11通过固相萃取（SPE）进行分离。血浆中总CPT - 11及主要代谢物7 - 乙基 - 10 - 羟基喜树碱（SN - 38）的含量通过超高效液相色谱 - 串联质谱法进行定量。校准曲线拟合良好，组织中SN - 38、游离CPT - 11、总CPT - 11和CPT - 11的定量下限分别为5 ng/ml、10 ng/ml、4.44 ng/ml和25 ng/ml。该方法的回收率、精密度和准确度均令人满意。利用此方法，随后研究了静脉注射2.5 mg/kg剂量的CPT - 11脂质体制剂后的药代动力学和生物分布。
