人血浆中特非那定的LC-MS 测定法

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (4): 432-435.

人血浆中特非那定的LC-MS 测定法

李丽敏¹, 郝彬²

¹上海市食品药品检验所, 上海 201203;
²上海交通大学药学院, 上海 200240

收稿日期:2009-03-12 修回日期:2009-04-13 发布日期:2020-10-29
作者简介:李丽敏,女,主管药师,主要研究方向为药物分析。Tel:021-38839900-26127 E-mail:chinalilymin@sohu.com

Determination of terfenadine concentration in human plasma by LCMS

LI Li-min¹, HAO Bin²

¹Shanghai Institute for Food and Drug Control, Shanghai 201203, China;
²School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China

Received:2009-03-12 Revised:2009-04-13 Published:2020-10-29

摘要/Abstract

摘要： 目的: 建立人血浆中特非那定的高效液相色谱-电喷雾质谱联用(HPLC ESI-MS)测定方法。方法: 以氟桂利嗪为内标,血浆以2 mol/L NaOH溶液碱化后,经乙酸乙酯提取;选用Phenomenex C₁₈色谱柱(250 mm ×4.6 mm,5 μm),柱温25 ℃;流动相为甲醇-水80∶20(含1 %的冰醋酸和0.5 %的三乙胺),流速1 mL/min ;采用四级杆电喷雾质谱检测器进行定量,选择性正离子检测(SIM),特非那定m z 472,氟桂利嗪m z 203 。结果: 本法线性范围为0.1 ～ 20 ng/mL,最低检测限为0.05 ng mL(S N >3),血浆中特非那定的日内和日间精密度为2.54 % ～ 9.28 %,回收率为88.62 %～ 91.67 %。结论: 本法专属性强、灵敏度高,适用于临床试验中特非那定的药代动力学研究。

关键词: 特非那定, 高效液相色谱-质谱, 血浆, 测定

Abstract: AIM: To establish a highly sensitive method for the quantitation of terfenadine in human plasma by using high performance liquid chromatogramelectrospray ionization-mass spectrometry (LC-ESIMS).METHODS: Flunarizine was chosen as the internal standard (I.S.) , the plasma was extracted by ethyl acetate after alkalized with 2 mol L sodium hydroxide, and the Phenomenex C18 chromatographic column(250 mm ×4.6 mm, 5 μm) was used, the column temperature was 25 ℃, the mobile phase was methanol-water(80∶20) including 1 %glacial acetic acid and 0.5 % triethylamine.The flow rate was 1 mL/min.Analytes were quantitated using positive electrospray ionization in a quadrupole spectrometer.The selected ion monitoring(SIM) mode was detected , terfenadine m z was 472 and flunarizine m z was 203.RESULTS: The linear range was 0.1 -20 ng mL, the lowest detectable limit was 0.05 ng mL (S N >3) , The intra and inter-assay precision of terfenadine was 2.54 %-9.28 %.The recovery of terfenadine in plasma was 88.62 % -91.67 %.CONCLUSION: The method has strong specificity and high sensitivity and can be used for clinical experiment of terfenadine pharmacokinetic study.

Key words: terfenadine, HPLC-MS, plasma, determination

中图分类号:

R969.1

李丽敏, 郝彬. 人血浆中特非那定的LC-MS 测定法[J]. 中国临床药理学与治疗学, 2009, 14(4): 432-435.

LI Li-min, HAO Bin. Determination of terfenadine concentration in human plasma by LCMS[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(4): 432-435.

参考文献

[1] 张群芳, 陈天瑞.抗组胺新药特非那定(terfenadine)的药理和临床概况[J].医药导报, 1991, 10(3):1-3.
[2] Sorkin EM, Heel RC.Terfenadine.A review of its pharmacodynamics properties and therapeutic efficacy [J].Drugs, 1985, 29(1):34-56.
[3] Cook CE, Williams DL, Myers M, et al.Radioimmunoassay for terfenadine in human plasma[J].J Pharm Sci,1980, 69(12):1419-1423.
[4] Surapaneni S, Khalil SKW.A sensitive HPLC method for the determination of terfenadine and its metabolite in human plasma[J].J Liq Chromatogr, 1994, 17(11):2419-2428.
[5] Coutant JE, Westmark PA, Nardella PA, et al.Determination of terfenadine and terfenadine acid metabolite in plasma using solid-phase extraction and high-performance liquid chromatography with fluorescence detection[J].J Chromatogr, 1991, 570(1):139-148.
[6] Terhechte A, Blaschke G.Investigation of the stereoselective metabolism of the chiral H1-antihistaminic drug terfenadine by high-performance liquid chromatography[J].J Chromatogr A, 1995, 694(1):219-225.
[7] Argekar AP, Shah SJ, Raj SV.Simultaneous determination of pseudoephidrine HCl (PSE)and terfanidine (TER)from formulations by reversed-phase ion pair high-performance liquid chromatography (RP-HPLC)[J].Drug Dev Ind Pharm, 1998, 24(3):219-223.
[8] Martens J.Determination of the terfenadine metabolite azacy clonol in human serum using gas chromatographymass spectrometry [J].J Chromatogr B Biomed Appl, 1996, 678(2):349-353.
[9] Chen TM, Chan KY, Coutant JE, et al.Determination of the metabolites of terfenadine in human urine by thermospray liquid chromatography-mass spectrometry [J]. J Pharm Biomed Anal, 1991, 9(10 11 12):929-933.
[10] Ghoneim M, Issa R, Tawfik A.Assay of terfenadine in pharmaceutical formulation and human plasma by adsorptive stripping voltammetry [J].J Pharm Biomed Anal,2001, 26(4):593-598.

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