目的: 采用HPLC 法测定三氟柳（TFL）及其活性代谢产物HTB 的血药浓度、尿药浓度。方法: 采用岛津公司2010 型HPLC 仪, 紫外检测波长为234 nm, 萘普生作内标。色谱柱为YMC C18（150 mm×4. 6 mm, 5 μm）, 流动相为甲醇-水-甲酸（75∶25∶0. 1, ）, 流速0. 78 mL·min-1, 柱温30 ℃。血浆和尿液样本酸化后经二氯甲烷萃取后挥干复溶进样。结果: 所建方法经验证, TFL、HTB 的血浆标准曲线范围分别为20~0. 5、200~5 μg·mL-1, 尿液标准曲线范围分别为200~5、40~1 μg·mL-1, 其线性、准确度、精密度、定量下限、提取回收率、特异性、稳定性等指标均符合NMPA 的指导原则要求。12 例受试者单次口服TFL 胶囊（含TFL 600mg）后, 用所建方法检测了经时血药浓度和尿药浓度, 结果可靠。结论: 本法稳定可靠, 可用于TFL、HTB的血药、尿药浓度测定和体内药代动力学研究。
Objective: To establish an HPLC method for determination of triflusal（TFL）and its major active metabolite 2-hydroxy-4-trifluoromethyl benzoic acid（HTB）in human plasma and urine. Methods: Shimadzu 2010 series HPLC was used and the UV detector wavelength was set at 234 nm. Naproxen was used as an internal standard（IS）. Urine and plasma samples were extracted by dichloromethane after acidized. The extraction solution was dried, re-dissolved and separated on a YMC C18 column（150 mm×4. 6 mm, 5 μm）. Mobile phase was methanol-water-formic acid（75∶25∶0. 1）and the flow rate was 0. 78 mL·min-1. The column oven was set at 30 ℃. Results: In plasma, the calibration curves for TFL was in the range of 20-0. 5 μg·mL-1, for HTB was in the range of 200-5 μg·mL-1. In urine, the calibration curves for TFL was in the range of 200-5 μg·mL-1, for HTB was in the range of 40-1 μg·mL-1. The linear, accuracy, precision, limit of quantitation（LOQ）, extraction recovery, specificity, stability of our method meets the requirements by National medical products administration（NMPA）. After a single oral administration of TFL capsule（containing TFL 600 mg）in 12 subjects, the method was used to detect the plasma and urine concentrations, and the results were reliable. Conclusion: The method was suitable for the determination of Triflusal and its major active metabolite HTB in human plasma and urine.
[1] MCNEELY W, GOA KL. Triflusal[J]. Drugs, 1998, 55(6): 823
[2] MURDOCH D, PLOSKER GL. Triflusal, a review of its use in cerebral infarction and myocardial infarction, and as thromboprophylaxis in atrial fibrillation[J]. Drugs, 2006, 66(5): 671
[3] HECTOR A, GEORGE A, SOCRATES P, et al. Triflusal: an old drug in modern antiplatelet therapy. Review of its action, use, safety and effectiveness[J]. Hellen J Cardiol, 2009, 50(3): 199
[4] 夏杨, 张洪恩. 三氟柳抗血小板活化作用及机制研究[J]. 安徽医药, 2008(10): 897
XIA Y, ZHANG HE. Study on antiplatelet activation and its mechanism of triflusal[J]. Anhui Med Pharm J, 2008(10): 897
[5] 曲东锋. 三氟柳和阿司匹林在脑梗死预防方面的比较[J]. 国外医学(脑血管疾病分册), 2004, 12(5): 363
QU DF. Comparison of t triflusal and aspirin in the prevention of cerebral infarction[J]. Foreign Med Sci(Cerebrovasc Dis), 2004, 12(5): 363
[6] 李宏建. 三氟柳和阿司匹林对急性缺血性卒中患者炎症标志物的不同作用[J]. 国际脑血管病杂志, 2009, 17(11): 804
LI HJ. Different effects of triflusal and aspirin on inflammatory markers in patients with acute ischemic stroke[J]. Intern J Cerebrovasc Dis, 2009, 17(11): 804
[7] 李宏建. 三氟柳与阿司匹林在动脉粥样硬化血栓形成事件二级预防中的比较[J]. 国际脑血管病杂志, 2018, 26(08): 598
LI HJ. Comparison of triflusal and aspirin in secondary prevention of atherosclerotic thrombus events[J]. Intern J Cerebrovasc Dis, 2018, 26(8): 598
[8] The European Stroke Organization(ESO)Executive Committee and the ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008[J]. Cerebrovasc Dis, 2008, 25(5): 457
[9] RAMIS J, MIS R, FORN J, et al. Pharmacokinetics of triflusal and its main metabolite HTB in healthy subjects following a single oral dose[J]. Eur J Drug Metabol Pharmacok, 1991, 16(4): 269
[10] QUETGLAS EG, CAMPANERO MA, SADABA B, et al. Bioequivalence of two oral formulation of triflusal capsules in healthy volunteers[J]. Arzneimittel-Forschung(Drug Res), 2008, 58(6): 283
[11] IZQUIERDO I, BORJIA J, ROVIRA S, et al. Comparative bioavailability study of triflusal oral solution vs. triflusal capsules in healthy subjects. A single, randomized, two-way cross-over, openlabel phase I study[J]. Arzneimittelforschung, 2010, 60(1): 36
[12] 马晓敏, 邹梅娟, 苗苗, 等. 三氟柳胶囊在中国健康志愿者体内的药动学研究[J]. 沈阳药科大学学报, 2014;31(5): 401
MA XM, ZOU MJ, MIAO M, et al. Study on pharmacokinetics of triflusal capsules in Chinese healthy volunteers[J]. J Shenyang Pharm Univ, 2014, 31(5): 401
[13] 彭莉, 丁莉坤, 贾艳艳, 等. 三氟柳胶囊单剂量与多剂量人体药动学研究[J]. 中国药房, 2015;26(35): 4934
PENG L, DING LK, JIA YY, et al. Pharmacokinetic study on single dose and multiple dose of triflusal capsule in healthy volunteers[J]. China Pharm, 2015, 26(35): 4934
[14] CHO HY, JEONG TJ, LEE YB. Simultaneous determination of triflusal and its major active metabolite, 2-hydroxy-4-trifluoromethyl benzoic acid, in rat and human plasma by high-performance liquid chromatography[J]. J Chromatogr B, 2003, 798(2): 257
[15] 钱亚芳, 丁黎, 潘丽萍, 等. LC-MS 法测定人血浆中的三氟柳及其活性代谢物2-羟基-4-三氟甲基苯甲酸[J]. 药物分析杂志, 2014, 34(9): 1541
QIAN YF, DING L, PAN LP, et al. Determination of triflusal and its active metabolite 2-hydroxy-4-(trifluoromethyl)benzoic acid in human plasma by LC-MS[J]. Chin J Pharm Anal, 2014, 34(9): 1541
[16] 彭莉, 丁莉坤, 贾艳艳, 等. LC-MS/MS 法测定人血浆中三氟柳浓度及药动学[J]. 中国新药杂志, 2015, 24(1): 27
PENG L, DING LK, JIA YY, et al. Determination of triflusal in human plasma by LC-MS/MS and its pharmacokinetics[J]. Chin J New Drugs, 2015, 24(1): 27
[17] 中华人民共和国药典2015年版. 四部[S]. 2015: 363
ChP 2015. hP 2015. Vol Ⅳ[S]. 2015: 363
