VND3207及其代谢产物在大鼠体内的药代动力学

目的建立液质联用(HPLC-MS/MS)方法,同时测定血浆中VND3207及其代谢产物的浓度并探讨VND3207在大鼠体内的药代动力学。方法 SD大鼠ig给予VND3207 70 mg.kg-1后,于不同时间点采集血样,血浆样品经C18反相液相色谱柱梯度洗脱,采用串联质谱正离子检测多反应监测模式对VND3207及其代谢产物丁香酸和丁香醇进行定量分析,计算VND3207及其代谢产物的药代动力学参数。结果 VND3207、丁香酸和丁香醇的定量线性范围均为2～2000μg.L-1,最低定量下限为2μg.L-1,日内和日间精密度CV均<15%,准确度为91.2%～110.7%。通过测定SD大鼠ig给予VND3207 70 mg.kg-1后12 h的血药浓度,计算VND3207,丁香酸和丁香醇药时曲线下面积(AUC0-∞)分别为19.37±10.56,1825.32±719.97和(9.89±1.75)mg.L-1.min;消除半衰期(T1/2)分别为78.0±44.6,114.4±17.9和(66.0±23.8)min。结论 建立了快速、灵敏、准确地同时定量大鼠血浆中VND3207,丁香酸和丁香醇液质联用分析方法。VND3207被大鼠快速吸收,其中大量VND3207被氧化为丁香酸,少量被还原为丁香醇。

Pharmacokinetics of VND3207 and its metabolites in rats

OBJECTIVE To develop a quick, sensitive and accurate high performance liquid chromatography tandem mass spectrometric(HPLC-MS/MS) method for quantification of VND3207 and its metabolites in rat plasma and to investigate pharmacokinetics of VND3207 in SD rats. METHODS Rats were ig given VND3207 70 mg·kg^-1. Blood samples were collected and separated by liquid chromatography on a C18 reversion phase chromatographic column with gradient elution. Concentration of VND3207 and its metabolites syringic acid and syringic alcohol were detected by HPLC-MS/MS in positive multiple reaction monitoring mode. Pharmacokinetic parameters of VND3207 and its metabolites were calculated. RESULTS Calibration curves of VND3207 and its metabolites syringic acid and syringic alcohol were linear within the range of 2-2000 μg·L^-1, ranged from quantification limit 2 μg·L^-1. Intra- and inter-day precision was both less than 15%, and accuracy with 91.2%-110.7%. The concentrations of VND3207 and its metabolites were detected in plasma of rats up to 12 h after VND3207 was ig given to rats. AUC_0-∞ of VND3207, syringic acid and syringic alcohol were 19.37±10.56, 1825.32±719.97 and (9.89±1.75) mg·L^-1·min, and T_1/2 was 78.0±44.6, 114.4±17.9 and (66.0±23.8)min, respectively. CONCLUSION A quick, sensitive and accurate HPLC-MS/MS method is developed for quantification of VND3207 and its metabolites in rat plasma. VND3207 is absorbed and metabolized rapidly. A large amount of VND3207 is oxidized to syringic acid while a small amount is reduced to syringic alcohol.