Pin Huang, Hong-Min Lu, Ming Ye, Qin Li
Department of Clinical Pharmacology, Shanghai New Drugs Research and Development Center, Shanghai, China.
Biomed Chromatogr. 2012 Jul;26(7):797-801. doi: 10.1002/bmc.1731. Epub 2011 Nov 20.
A rapid, simple and sensitive LC-MS/MS method for the quantification of vinflunine in plasma was developed and validated. The analysis involved a simple liquid-liquid extraction. After making alkaline with NaOH, plasma was extracted with methyl tert-butyl ether and the organic extract was then evaporated and the residue was reconstituted in mobile phase. The reconstituted solution was injected into an HPLC system and was subjected to reverse-phase HPLC on a 5 µm ODS-3 column at a flow-rate of 0.2 mL/min. The mobile phase consisted of ammonium acetate (0.02 mol/L, pH = 3.0) and acetonitrile (20:80). Vinflunine was detected in the single ion monitoring mode using target ions at m/z 817.4/160.1/142.3 for vinflunine and m/z 447.2/128.3/112.1 for gefitinib (internal standard). Standard curves were linear over the concentration range of 5-1000 ng/mL. The mean predicted concentrations of the quality control samples deviated by less than 2% from the corresponding nominal values; the intra-assay and inter-assay precisions of the assay were within 7% relative standard deviation. The extraction recovery of vinflunine was more than 80%. The validated assay was applied to a pharmacokinetic study of vinflunine in plasma following the administration of a single vinflunine injection (2 mg/kg).
建立并验证了一种快速、简单且灵敏的液相色谱-串联质谱法用于定量测定血浆中的长春氟宁。该分析采用简单的液-液萃取法。用氢氧化钠碱化后，血浆用甲基叔丁基醚萃取，然后将有机萃取液蒸发，残渣用流动相复溶。复溶后的溶液注入高效液相色谱系统，在5 µm ODS-3柱上以0.2 mL/min的流速进行反相高效液相色谱分析。流动相由醋酸铵（0.02 mol/L，pH = 3.0）和乙腈（20:80）组成。采用单离子监测模式检测长春氟宁，长春氟宁的目标离子为m/z 817.4/160.1/142.3，吉非替尼（内标）的目标离子为m/z 447.2/128.3/112.1。标准曲线在5-1000 ng/mL的浓度范围内呈线性。质控样品的平均预测浓度与相应标称值的偏差小于2%；该测定法的批内和批间精密度的相对标准偏差均在7%以内。长春氟宁的萃取回收率超过80%。将经验证的测定法应用于单次注射长春氟宁（2 mg/kg）后血浆中长春氟宁的药代动力学研究。
