徐晓燕, 张蕊, 袁桂艳, 王本杰, 刘晓燕, 郭瑞臣. HPLC-MS/MS法测定人体色甘酸钠血浆浓度及其药代动力学研究J. 药学学报, 2008, 43(9): 942-945.
引用本文: 徐晓燕, 张蕊, 袁桂艳, 王本杰, 刘晓燕, 郭瑞臣. HPLC-MS/MS法测定人体色甘酸钠血浆浓度及其药代动力学研究J. 药学学报, 2008, 43(9): 942-945.
XU Xiao-yan, ZHANG Rui, YUAN Gui-yan, WANG Ben-jie, LIU Xiao-yan, GUO Rui-chen. HPLC-MS/MS method for determination of sodium cromoglycate concentration in human plasma and its pharmacokineticsJ. Acta Pharmaceutica Sinica, 2008, 43(9): 942-945.
Citation: XU Xiao-yan, ZHANG Rui, YUAN Gui-yan, WANG Ben-jie, LIU Xiao-yan, GUO Rui-chen. HPLC-MS/MS method for determination of sodium cromoglycate concentration in human plasma and its pharmacokineticsJ. Acta Pharmaceutica Sinica, 2008, 43(9): 942-945.

HPLC-MS/MS法测定人体色甘酸钠血浆浓度及其药代动力学研究

HPLC-MS/MS method for determination of sodium cromoglycate concentration in human plasma and its pharmacokinetics

  • 摘要: 采用HPLC-MS/MS法测定人血浆中色甘酸钠浓度,进行其滴鼻液和鼻用喷雾剂的药代动力学研究并评价其生物等效性。采用高效液相分离系统,流动相为乙酸铵-甲醇(含50%乙腈)(15∶85),固定相为AGT Venusil XBP C18(250 mm×4.6 mm ID, 5 μm)色谱柱。采用质谱检测系统, ESI离子源, 正离子模式, 多级反应监测(MRM)方式, m/z 469→263.1(色甘酸钠), m/z 447.2→327.1(内标,普伐他汀钠)。在0.3~20 ng·mL-1色甘酸钠血药浓度呈线性关系, 定量限为0.3 ng·mL-1, 回收率在94.1%以上, 日内日间的RSD均小于14.3%。单剂量给药色甘酸钠鼻用喷雾剂或滴鼻液, 其药代动力学参数T1/2分别为(1.82±0.54)和(1.59±0.52) h; Tmax分别为(0.47±0.12)和(0.44±0.15) h; Cmax分别为(9.79±4.66)和(10.88±4.05) ng·mL-1, AUC0-5 h分别为(11.52±3.46)和(12.63±4.23) ng·mL-1·h。色甘酸钠鼻用喷雾剂相对生物利用度Fr为(93.6±13.8)%。本法灵敏度高, 适用于色甘酸钠治疗药物监测及其药代动力学和生物利用度研究。

     

    Abstract: The study established an HPLC-MS/MS method for determining the concentrations of sodium cromoglycate in human plasma and evaluated the pharmacokinetics of nasal drops and nasal spray. A C18 column was used to separate sodium cromoglycate in plasma with a mobile phase of a mixture of ammonium-methanol (involves 50% acetonitrile) (15∶85) at a flow rate of 0.4 mL·min-1. Electronic spray ionization (ESI) and multiple-reaction monitoring (MRM) were used for the determination of sodium cromoglycate in human plasma. The linear range of the standard curve of sodium cromoglycate was from 0.3 to 20 ng·mL-1, and the minimum concentration of detection was 0.3 ng·mL-1. The extraction recovery was more than 94.1%, intra-day and inter-day RSD were less than 14.3%. After a single dose of sodium cromoglycate, the main pharmacokinetic parameters of nasal spray and nasal drops were as follows, T1/2 (1.82±0.54) h, (1.59±0.52) h; Tmax (0.47±0.12) h, (0.44±0.15) h; Cmax (9.79±4.66) ng·mL-1, (10.88±4.05) ng·mL-1; AUC0-5 h (11.52±3.46) ng·mL-1·h, (12.63±4.23) ng·mL-1·h, Fr (93.6±13.8)%. The method is sensitive, rapid and accurate. It is suitable for therapeutic drug monitoring and human pharmacokinetic study of sodium cromoglycate.

     

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