目的 研究不同拉西地平固体分散体在Beagle犬体内的药动学和生物等效性。方法 采用Thermo C₁₈色谱柱（50 mm×2.1 mm，2.6μm）；流动相：0.2%甲酸水溶液–乙腈（17∶83）；体积流量：0.2 mL/min；柱温：30℃；进样室温度：15℃；进样量：10 μL。采用电喷雾离子源（ESI），多反应监测（MRM）方式扫描，以正离子方式进行检测；用于定量分析的离子对分别为拉西地平m/z 473.47（母离子）→354.28（子离子），内标尼莫地平m/z 419.25（母离子）→343.18（子离子）。6只健康Beagle犬分别给予4 mg参比制剂拉西地平片（R）、拉西地平-HPMC E5固体分散体（T₁）和拉西地平-Soluplus固体分散体（T₂），绘制血药浓度–时间曲线，采用DAS 2.1.1软件非隔室模型计算主要药动学参数，并进行生物等效性分析。结果 拉西地平在0.25～100 ng/mL线性关系良好，定量下限为0.25 ng/mL。在0.5、5.0、80.0 ng/mL的提取回收率和基质效应分别为100.92%～102.89%和100.71%～102.89%，RSD值<11%。T₁、T₂和R的主要动力学参数分别为峰浓度（C_max）为（24.45±6.53）、（28.80±11.89）、（26.647±4.44）ng/mL；达峰时间（t_max）为（1.13±0.70）、（1.29±0.64）、（1.79±1.36）h；t_1/2分别为（8.39±4.60）、（7.10±6.73）、（5.20±6.16）h。受试制剂相对生物利用度为（112.2±57.8）%、（110.6±51.6）%。生物等效性分析两组受试制剂与参比制剂均不具备生物等效性。结论 该方法准确、灵敏度高、专属性强，可用于拉西地平制剂的药动学和生物等效性研究。自制拉西地平固体分散体与市售拉西地平片生物等效性不一致。

Objective To study the pharmacokinetics and bioequivalence of different lacidipine solid dispersions in Beagle dogs. Methods The separation was carried out on Thermo C₁₈ chromatography column (50 mm×2.1 mm, 2.6 μm). The mobile phase consisted of 0.2% formic acid aqueous solution and acetonitrile (17:83). The flow rate was 0.2 mL/min, temperature of column was set at 30℃, the temperature of injection chamber was 15℃, and volume of injection was 10 µL. Electrospray ionization (ESI) source and multiple-reaction monitoring (MRM) was performed in the positive ion mode. The ion pairs of m/z 473.47→354.28 and m/z 419.25→343.18 were used to lacidipine and internal standard nimodipine. Six Beagle dogs were ig administered with 4 mg reference preparation Lacidipine Tablets (R), Lacidipine-HPMC E5 solid dispersion (T₁), and Lacidipine-Soluplus solid dispersion (T₂), respectively, and plasma concentration-time curves were obtained. The main pharmacokinetic parameters were calculated by non-compartment model of DAS 2.1.1 software, and the bioequivalence was analyzed. Results The linear ranges of lacidipine were 0.25-100 ng/mL with the lower limit of quantification (LLOQ) of 0.25 ng/mL. Under concentrations of 0.5, 5.0, and 80.0 ng/mL, the extraction recovery and matrix effect were 100.92%-102.89% and 100.71%-102.89%, respectively, RSD < 11%. The main pharmacokinetic parameters of reference preparation (R) and test preparation (T_1, T₂) were as following:the peak concentration (C_max) were (24.45 ±6.53), (28.80 ±11.89), and (26.647 ±4.44) ng/mL; time to reach peak concentration (t_max) were (1.13 ±0.70), (1.29 ±0.64), and (1.79 ±1.36) h; t_1/2 were (8.39 ±4.60), (7.10 ±6.73), and (5.20 ±6.16) h. The relative bioavailability of the tested preparation were (112.2 ±57.8)% and (110.6 ±51.6)%. Conclusion The method is accurate, sensitive, and specific, and can be used to study the pharmacokinetics and bioequivalence of lacidipine preparations. The bioequivalence of the self-made lacidipine solid dispersion is not consistent with that of the commercial preparation Lacidipine Tablets.