药学学报, 2018, 53(1): 121-126
引用本文:
沈佳乐, 昝斌, 陈笑艳, 钟大放. LC-MS/MS法同时测定人血浆中福沙匹坦和代谢物阿瑞匹坦[J]. 药学学报, 2018, 53(1): 121-126.
SHEN Jia-le, ZAN Bin, CHEN Xiao-yan, ZHONG Da-fang. Simultaneous determination of fosaprepitant and its metabolite aprepitant in human plasma by liquid chromatography-tandem mass spectrometry[J]. Acta Pharmaceutica Sinica, 2018, 53(1): 121-126.

LC-MS/MS法同时测定人血浆中福沙匹坦和代谢物阿瑞匹坦
沈佳乐1,2, 昝斌2, 陈笑艳2, 钟大放1,2
1. 浙江工业大学药学院, 浙江 杭州 310014;
2. 中国科学院上海药物研究所, 上海 201203
摘要:
建立了LC-MS/MS法同时测定人血浆中福沙匹坦及其代谢物阿瑞匹坦,并应用于中国健康受试者的药动学研究。本法中血浆样品以乙腈沉淀蛋白处理,经Cortex C18+色谱柱(50 mm×2.1 mm,2.7 μm)分离,以甲醇-10 mmol·L-1醋酸铵(含0.1 mmol·L-1 EDTA)为流动相。采用电喷雾离子源(ESI源),以多反应监测负离子模式检测。以稳定同位素标记内标d4-福沙匹坦和d4-阿瑞匹坦分别作为福沙匹坦和阿瑞匹坦的内标,用于定量分析的离子反应分别为m/z 613.1→78.9(福沙匹坦)、m/z 617.0→78.9(d4-福沙匹坦)、m/z 533.2→275.1(阿瑞匹坦)和m/z 537.2→279.1(d4-阿瑞匹坦)。由于福沙匹坦为阿瑞匹坦的磷酸化前药,在血浆中快速降解,所以实验中采用碱性缓冲液处理血浆以确保其稳定。测定福沙匹坦标准曲线线性范围为15~6 000 ng·mL-1;测定阿瑞匹坦标准曲线线性范围为10~4 000 ng·mL-1。各待测物的日内、日间精密度和准确度均符合生物样品分析相关要求。该方法经验证后,成功应用于12名中国健康受试者静脉滴注150 mg福沙匹坦双葡甲胺后药动学研究。
关键词:    LC-MS/MS      福沙匹坦      阿瑞匹坦      稳定性      人体药动学     
Simultaneous determination of fosaprepitant and its metabolite aprepitant in human plasma by liquid chromatography-tandem mass spectrometry
SHEN Jia-le1,2, ZAN Bin2, CHEN Xiao-yan2, ZHONG Da-fang1,2
1. College of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China;
2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Abstract:
An LC-MS/MS method was developed for the simultaneous determination of fosaprepitant and aprepitant in human plasma, and applied to a pharmacokinetic study of 150 mg fosaprepitant dimeglumine injection to 12 Chinese healthy volunteers. The analytes and internal standards were extracted from plasma by protein precipitation with acetonitrile and separated on a Cortex C18+ (50 mm×2.1 mm, 2.7 μm) column using a gradient elution procedure. Mass spectrometry was performed in negative MRM mode, and parent-to-produce transitions were as follows:m/z 613.1→78.9 for fosaprepitant, m/z 617.0→78.9 for d4-fosaprepitant, m/z 533.2→275.1 for aprepitant and m/z 537.2→279.1 for d4-aprepitant. Plasma sample was basified to stabilize fosaprepitant. The standard curves were demonstrated to be liner in the range of 15.0 to 6 000 ng·mL-1 for fosaprepitant and 10.0 to 4 000 ng·mL-1 for aprepitant. The intra-day precisions and inter-day precisions and accuracy were within the acceptable limits for all concentrations.
Key words:    LC-MS/MS    fosaprepitant    aprepitant    stability    human pharmacokinetics   
收稿日期: 2017-08-14
DOI: 10.16438/j.0513-4870.2017-0788
基金项目: 国家自然科学基金资助项目(81521005).
通讯作者: 钟大放,Tel/Fax:86-21-50800738,E-mail:dfzhong@mail.shcnc.ac.cn
Email: dfzhong@mail.shcnc.ac.cn
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参考文献:
[1] Aapro M, Carides A, Rapoport BL, et al. Aprepitant and fosaprepitant:a 10-year review of efficacy and safety[J]. Oncologist, 2015, 20:450-458.
[2] Vania M, Amy G, Veronica A. Aprepitant:a new modality for the prevention of postoperative nausea and vomiting:an evidence-based review[J]. J Peroans Nur, 2015, 30:406-417.
[3] Azuma J, Fukase H. Pharmacokinetics of a single 150-mg intravenous infusion of fosaprepitant:effects of concentration and infusion time in healthy Japanese men[J]. Clin Pharm Drug Dev, 2013, 2:394-399.
[4] Lasseter KC, Gambale J, Jin B, et al. Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects[J]. J Clin Pharmacol, 2007, 47:834-840.
[5] Xu MJ, Chu JH, Wu T, et al. One kind of plasma fosaprepitant and aprepitant simultaneous detection:CN 105974016 A[P]. 2016-09-28.
[6] Skrdla J, Abrahim A, Wu Y. An HPLC chromatographic reactor approach for investigating the hydrolytic stability of a pharmaceutical compound[J]. J Pharm Biomed Anal, 2006, 41:883-890.
[7] European Medicines Agency. Guideline on Bioanalytical Method Validation[S]. 2011-07-21[2017-08-14]. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/08/WC500109686.pdf.
[8] Chinese Pharmacopoeia Commission. Pharmacopoeia of the People's Republic of China (中华人民共和国药典)[S]. 2015 ed. Vol 4. Beijing:China Medical Science Press, 2015:363-368.
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