经皮给药后尼索地平在大鼠体内血药浓度的LC-MS法测定

Determination of Nisoldipine in Rat Plasma after Transdermal Administration by LC-MS

建立了液相色谱-质谱法测定大鼠血浆中的尼索地平，并考察尼索地平微乳凝胶经皮给药后在大鼠体内的药动学。采用电喷雾离子源（ESI源），正离子检测，选择离子监测（SIM），监测离子对为m／z411（尼索地平）和m／z441（尼莫地平，内标）。血浆中尼索地平在O．5～50ng／ml浓度范围内线性关系良好，方法回收率为95％～102％，RSD≤5．8％。血浆中药物的提取回收率大于70％。采用雄性SD大鼠考察微乳凝胶经皮给药后的体内药动学行为并与口服混悬剂进行比较。含尼索地平20mg的微乳凝胶经皮给药后的主要药动学参数分别为tmax（42．00±6．92）h，cmax（27．53±1．88）ng／ml，AUC0-72h（1736.31±106．59）ng·h·ml-1，AUC0-∞（1999．66±119．26）ng·h·ml-1，MRT（44．02±0．77）h和t1/2（7．61±0．70）h。

A LC-MS method was established for the determination of nisoldipine in rat plasma and the pharmacokinetics of nisoldipine in rats was studied after transdermal administration of a microemulsion-based hydrogel. The electrospray ionization （ESI） was employed and the positive selected ion monitoring （SIM） mode was chosen. The ion combination of m/z 411 and m/z 441 was used to qualify nisoldipine and the internal standard （nimodipine）, respectively. The method recoveries were 95 % - 102 %, with RSDs no more than 5.8 %. The extractive recoveries were above 70 %. Male SD rats were employed to evaluate the pharmacokinetic behaviors of the microemulsion-based hydrogel after transdemal administration. The pharmacokinetics of the hydrogel and oral suspension were compared. After transdermal administration of the microemulsion-based hydrogel （containing 20 mg nisoldipine）, the main pharmacokinetic parameters were as follows： tmax （42.00±6.92） h, Cmax （27.53±1.88） ng/ml, AUC0-72 h （1 736.31±106.59） ng h ml-1, AUC0-∞ （1 999.66±119.26） ng h ml-1 MRT （44.02±0.77） h and t,/2 （7.61±0.70） h.