Clinical Pharmacology Research Center, Peking Union Medical College Hospital and Chinese Academy of Medical Sciences, Beijing 100730, China.
J Chromatogr A. 2013 Feb 1;1275:61-9. doi: 10.1016/j.chroma.2012.12.026. Epub 2012 Dec 22.
Vincristine sulfate liposome is a liposomal formulation of vincristine sulfate, a traditional anticancer drug, encapsulated in the aqueous core of phospholipid/cholesterol liposomes, which are kinds of targeted carriers to enhance malignancy targeting, exposure and anticancer activity of the drug. To evaluate and compare the pharmacokinetics of nonliposomal and liposome-encapsulated VCR and pharmacodynamic relationships associated with the toxicity and the efficacy behavior, it is essential to have a reliable method of separating the free and liposomal forms of the drug. In this paper, we have developed and validated methods to quantify the free vincristine (F-VCR) and total vincristine (T-VCR) in human plasma after intravenous administration of vincristine sulfate liposome injection (VSLI). The methods involve solid-phase extraction (SPE) for separating the F-VCR and liquid-liquid extraction (LLE) for releasing the VCR totally from the liposomal forms followed by an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). The methods were validated over the concentration range of 0.2-50 ng/mL for F-VCR and 0.5-400 ng/mL for T-VCR, respectively. Inter- and intra-day precision (RSD%) were ≤4.7% for F-VCR and ≤9.8% for T-VCR, respectively. The accuracies were between -2.3 and 9.1% for F-VCR and between -3.2 and 6.9% for T-VCR, respectively. The extraction recovery and the matrix effect were investigated. The methods were successfully applied to the pharmacokinetic study of VSLI in Chinese subjects with lymphoma.
硫酸长春新碱脂质体是硫酸长春新碱的脂质体制剂，硫酸长春新碱是一种传统的抗癌药物，被包裹在磷脂/胆固醇脂质体的水核中，脂质体是增强恶性肿瘤靶向性、暴露性和抗癌活性的靶向载体。为了评估和比较非脂质体和脂质体包封的长春新碱（VCR）的药代动力学和与毒性和疗效行为相关的药效学关系，必须有一种可靠的方法来分离游离形式和脂质体形式的药物。在本文中，我们开发并验证了一种方法，用于定量测定硫酸长春新碱脂质体注射液（VSLI）静脉给药后人血浆中的游离长春新碱（F-VCR）和总长春新碱（T-VCR）。该方法涉及固相萃取（SPE）分离游离长春新碱和液液萃取（LLE）从脂质体形式中完全释放长春新碱，然后采用超高效液相色谱串联质谱法（UHPLC-MS/MS）。检测在三重四极杆串联质谱仪上以正电喷雾电离（ESI）在多重反应监测（MRM）模式下进行。方法分别在 0.2-50ng/mL 范围内对 F-VCR 和 0.5-400ng/mL 范围内对 T-VCR 进行验证。F-VCR 的日内和日间精密度（RSD%）分别为≤4.7%，T-VCR 的日内和日间精密度（RSD%）分别为≤9.8%。F-VCR 的准确度在-2.3%至 9.1%之间，T-VCR 的准确度在-3.2%至 6.9%之间。考察了提取回收率和基质效应。该方法成功应用于中国淋巴瘤患者 VSLI 的药代动力学研究。
