HPLC法测定人唾液中卡马西平浓度及其药代动力学

Determination of carbamazepine concentration in human saliva by HPLC and its pharmacokinetic study

目的 :利用HPLC法测定人唾液中卡马西平浓度 ,并观察其药代动力学特征 .方法 :采用Shim packCLC ODSC1 8色谱分析柱 (1 5 0mm× 6mm ,5 μm) ,以甲醇 水 (5 3∶4 7)为流动相 ,流速为 1 .0mL·min-1 ,检测波长为 2 1 2nm ,柱温为室温 ,进样量 5 0 μL .根据唾液药物浓度求算 6名健康受试者单剂量口服卡马西平片剂的药代动力学参数 .结果 :本测定方法线形范围为 0 .4 0～ 4 .32mg·L-1 ,相关系数r =0 .999,最低检出浓度为 30 μg·L-1 (按S/N≥ 3计 ) ,方法平均回收率为99.1 7% - 1 0 4 . 80 % ;日内RSD、日间RSD分别在2 .6 % - 4 .9%和 3.0 % - 8.6 % .药动学参数表明 ,卡马西平人体内过程符合单室开放模型 ,Tmax,Cmax,ke,T1 / 2 ,AUC(0～inf) 分别为 (4 .5 0± 3.1 5 )h ,(1 .5 2± 0 .2 2 )mg·L-1 ,(0 .0 0 90± 0 .0 0 0 6 )h-1 ,(77.1 6± 5 .2 6 )h ,(1 32 .1 8± 8.82 )mg·h·L-1 .单次给药后 ,CBZ唾液浓度 时间曲线出现多峰现象 .结论 :该法简便、快速、专一性强 。

AIM: To determine carbamazepine(CBZ) concentration in human saliva by HPLC and study its pharmacokinetics. METHODS: Shim pack CLC ODS C 18 (150 mm×6 mm, 5 μm) spectrum analytical column was used and methanol water(53∶47)was adopted as the mobile phase. Flow rate was 1.0 mL·min -1 , detection wavelength was 212 nm, column temperature was 23℃ and the dosage of CBZ was 50 μL. The pharmacokinetic parameters of CBZ tablets taken by 6 healthy volunteers at a single oral dose of 200 mg were calculated according to CBZ concentration in saliva. RESULTS: The standard curve was linear ( r =0.999) within the range of 0.40～4.32 mg·L -1 for CBZ. The limit of detection in saliva was 30 μg·L -1 (S/N≥3). The average recovery was 99.17%-104.80%;the inter day RSD and intra day RSD was 2.6%-4.9% and 3.0% -8.6% respectively.The results showed that the pharmacokinetics of CBZ was in accordance with the one compartment open model. T max , C max , ke, T 1/2 and AUC (0～inf) was (4.50±3.15) h, (1.52±0.22) mg·L -1 , (0.0090±0.0006) h -1 , (77.16±5.26) h and (132.18± 8.82) mg ·h·L -1 respectively. After single dosing, the concentration time curve of CBZ in saliva presented multiple peaks. CONCLUSION: This method is simple, quick and specific, and can be used to determine CBZ concentration in human saliva and to study its pharmacokinetics.