目的：研究三氟柳胶囊在健康人体内的药动学特征。方法：采用单中心随机试验设计，将36 名健康受试者分为3 组，分别

单剂量口服三氟柳胶囊低、中、高剂量（300、600、900 mg），qd，给药当天进行单剂量人体药动学研究；中剂量组继续给药13 d，进行

多剂量人体药动学研究。采用液相色谱-串联质谱（LC-MS/MS）法测定三氟柳血药浓度，色谱柱为Zorbax SB-C18，流动相为甲

醇-0.2％甲酸水溶液（80 ∶20，V/V），流速为0.2 ml/min；采用电喷雾离子源（ESI），以多反应监测（MRM）模式扫描，负离子方式检测，

用于定量分析的离子对分别为m/z 247.1→161.1（三氟柳）、m/z 294.0→250.0（内标，双氯芬酸钠）。采用WinNonlin 6.2 软件计算药

动学参数，并比较其差异。结果：三氟柳血药浓度在0.05～20.0 μg/ml 范围内线性关系良好。单剂量低、中、高剂量组t1/2分别为

（0.45±0.20）、（0.47±0.10）、（0.43±0.20）h，tmax 分别为（0.56±0.20）、（0.60±0.20）、（0.47±0.40）h，cmax 分别为（3.30±0.98）、

（10.65±3.26）、（13.96±4.88）μg/ml，AUC0-8 h分别为（3.99±0.93）、（13.29±1.72）、（19.62±6.78）μg·h/ml，300～900 mg 剂量范围

内，cmax、AUC0-8 h与剂量呈线性关系（R2分别为0.954、0.986）。多剂量给药达稳态时，平均血药浓度为（0.71±0.20）μg/ml，AUCss为

（17.10±4.82）μg·h/ml，t1/2 为（0.49±0.10）h，tmax 为（0.85±0.62）h，cmax 为（11.58±3.99）μg/ml，AUC0-8 h 为（16.99±4.84）μg·h/ml，

AUC0-∞为（17.08±4.81）μg·h/ml，蓄积因子为（1.28±0.40）。单剂量给药与多剂量给药的tmax和t1/2相近。结论：LC-MS/MS法能快

速、准确地测定三氟柳在人体血浆中的浓度。三氟柳胶囊在健康受试者体内存在蓄积现象，且具线性药动学特征。

OBJECTIVE：To study the pharmacokinetic characteristics of triflusal capsule in healthy volunteers. METHODS：In randomized

test，36 healthy volunteers were randomly divided into 3 groups. They were given low-dose，medium-dose and high-dose of

Triflusal capsule（300 mg，600 mg and 900 mg），qd，for one day，and then pharmacokinetic study of single dose of Triflusal capsule

was conducted；Triflusal capsule medium-dose group was continuously given medicine for 13 days，and then pharmacokinetic study of

multiple dose of Triflusal capsule was conducted. The plasma concentration of triflusal was determined by LC-MS/MS，and Zorbax

SB-C18 column was used with methanol-0.2％ formic acid（80 ∶ 20，V/V）at the flow rate of 0.2 ml/min. ESI was adopted in MRM

mode，negative ion detection was carried out，quantitative analysis m/z 247.1→161.1（triflusal），m/z 294.0→250.0（internal standard，

diclofenac sodium）. Pharmacokinetic parameters were calculated by using WinNonlin 6.2 software，and the difference of them were

compared. RESULTS：The linear range of triflusal were 0.05-20 μg/ml. The main pharmacokinetic parameters of triflusal capsules

high-dose，medium-dose and low-dose groups were as follows：t1/2 were（0.45 ± 0.20），（0.47 ± 0.10），（0.43 ± 0.20）h；tmax were

（0.56±0.20），（0.60±0.20），（0.47±0.40）h；cmax were（3.30±0.98），（10.65±3.26），（13.96±4.88）μg/ml；AUC0-8 h were（3.99±0.93），

（13.29±1.72），（19.62±6.78）μg·h/ml；within dose of 300-900 mg，linear relationship was found between cmax，AUC0-8 h and dose（R2＝

0.954，0.986）. When reaching stable state of multiple dose，average blood concentration was（0.71±0.20）μg/ml；main pharmacokinetic

parameters were as follows：AUCss（17.10±4.82）μg·h/ml，t1/2（0.49±0.10）h，tmax（0.85±0.62）h，cmax（11.58±3.99）μg/ml，AUC0-8 h

（16.99±4.84）μg·h/ml，AUC0- ∞（17.08±4.81）μg·h/ml；accumulation factor（1.28±0.40）. tmax and t1/2 of single dose were similar to

those of multiple dose. CONCLUSIONS：LC-MS/MS can determine the content of triflusal in human plasma rapidly and accurately，

and accumulation phenomena exist in healthy Chinese volunteers，which shows linear pharmacokinetic characteristics.