目的 采用HPLC法研究缬沙坦纳米骨架系统在SD大鼠体内的生物利用度。方法 采用BDS Hypercil C₁₈柱（250 mm×4.6 mm，5 μm）；流动相：甲醇-乙腈-0.01 mol/L磷酸二氢钾（44：24：32）；体积流量1.0 mL/min；检测波长250 nm；柱温30℃；进样量20 μL。取雄性SD大鼠12只，随机分为2组，按照缬沙坦20 mg/kg分别ig缬沙坦胶囊和缬沙坦纳米骨架系统，绘制血药浓度-时间曲线，采用DAS 2.1.1软件计算主要动力学参数C_max、t_max、AUC、F。结果 缬沙坦在0.481~48.1 μg/mL线性关系良好。定量限为0.4 μg/mL，准确度、灵敏度、精密度和专属性均符合体内分析方法学要求。缬沙坦纳米骨架系统药时曲线下面积比缬沙坦胶囊提高154.78%，显著提高缬沙坦的体内生物利用度。结论 缬沙坦纳米骨架系统血药浓度变化相对较为平缓，有望成为难溶性药物的新型给药方式。

Objective To study the bioavailability of valsartan nanomatrix drug delivery system in SD rats by HPLC method. Methods BDS Hypercil C₁₈ column (250 mm×4.6 mm, 3 μm) was used. The mobile phase consisted of methanol-acetonitrile-0.01 mol/L potassium dihydrogen phosphate (44:24:32). The detection wavelengths were set at 250 nm. The flow rate was 1.0 mL/min, volume of injection was 20 μL, and temperature of column was set at 30℃. 12 Healthy male SD rats were randomly divided into two groups. According to the dose of valsartan 20 mg/kg, each group was ig administered with valsartan capsules or valsartan nanomatrix drug delivery system. The plasma concentration-time curve was drawn and the main kinetic parameters C_max, t_max, AUC, and F were calculated by DAS 2.1.1 software. Results The linear range of valsartan was 0.481-48.1 μg/mL. The limit of quantification was 0.4 μg/mL. The accuracy, sensitivity, precision, and specificity all meet the requirements of in vivo analysis methodology. The area under the curve of valsartan nanomatrix drug delivery system was 154.78%, which higher than that of valsartan capsules, and significantly improved the bioavailability of valsartan in vivo. Conclusion The change of blood drug concentration in valsartan nanomatrix drug delivery system is relatively gentle, and the nanomatrix drug delivery system is expected to become a promising way for insoluble drug delivery.

国家重大科学研究计划项目（2015CB932100）