目的 采用超高效液相色谱-串联质谱（UPLC-MS/MS）技术，对比研究补骨脂中11种活性成分在正常大鼠与骨质疏松模型大鼠体内的药动学特征，明确病理状态对补骨脂成分体内过程的影响，为补骨脂治疗骨质疏松的临床合理用药提供参考。方法 采用双侧卵巢摘除法构建雌性SD大鼠骨质疏松模型，同时设置假手术组； 2组大鼠均按临床等效剂量（1.07 g·kg^-1） ig给予补骨脂药液，分别于给药前及给药后多个时间点经眼眶静脉采集血样；通过UPLC-MS/MS技术定量检测血浆中11种补骨脂成分的血药浓度，采用DAS 3.0软件以非房室模型计算各成分的药动学参数，比较两组参数的统计学差异。结果 与假手术组相比，骨质疏松模型大鼠ig给予补骨脂后，多数成分的主要药动学参数发生显著改变：补骨脂素的血药浓度时间曲线下面积（AUC_0～t、AUC_0～∞）、平均滞留时间（MRT_0～∞）均显著降低（P＜0.05、0.001），提示其体内暴露水平降低、清除加快；异补骨脂素AUC_0～∞、AUC_0～t、峰浓度（C_max）、达峰时间（t_max）均显著降低（P＜0.05、0.01），提示吸收加快，但总暴露量与峰浓度下降；补骨脂酚、补骨脂甲素、巴库查尔酮、corylifol A、新补骨脂异黄酮的AUC相关指标显著降低（P＜0.05、0.01），体内暴露量减少；补骨脂乙素AUC_0～∞、AUC_0～t显著降低且t_max显著缩短（P＜0.05、0.01），提示吸收加快但吸收总量下降；仅补骨脂宁的各项药动参数无统计学差异。结论 骨质疏松病理状态会显著改变补骨脂中多数活性成分的体内过程，临床应用补骨脂治疗骨质疏松时，应充分考虑患者疾病状态的差异，必要时结合血药浓度监测实施个体化给药，以保障用药的安全性与有效性。

Objective To compare the pharmacokinetic characteristics of 11 active components in Psoraleae Fructus between normal and osteoporotic model rats using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and to clarify the impact of pathological conditions on the in vivo disposition of these components, thereby providing reference for rational clinical use of Psoraleae Fructus in treating osteoporosis. Methods Ovariectomized female SD rats were used to establish an osteoporosis model, with a sham-operated group as control. Both groups received an oral administration of Psoraleae Fructus extract at a clinically equivalent dose (1.07 g·kg^-1). Blood samples were collected via orbital venipuncture at multiple time points before and after dosing. Plasma concentrations of the 11 components were quantified by UPLC-MS/MS. Pharmacokinetic parameters were calculated using DAS 3.0 software based on a non-compartmental model, and statistical differences between the two groups were analyzed. Results In contrast to the sham-operated group, intragastric administration of Psoraleae Fructus in osteoporosis model rats led to significant changes in the major pharmacokinetic parameters of multiple constituents. The area under the plasma concentration-time curve (AUC_0～t, AUC_0～∞) and mean residence time (MRT_0～∞) of psoralen were significantly reduced (P < 0.05, 0.001), indicating decreased systemic exposure and accelerated clearance. For isopsoralen, AUC_0～t, AUC_0～∞, peak concentration (C_max), and time to peak (t_max) were all significantly lower (P < 0.05, 0.01), suggesting faster absorption but reduced total exposure and peak concentration. AUC-related parameters for bakuchiol, bavachin, bakuchalcone, corylifol A, and neobavaisoflavone were also significantly reduced (P < 0.05, 0.01), indicating decreased systemic exposure. For isobavachalcone, both AUC_0～t and AUC_0～∞ were significantly reduced, and t_max was significantly shortened (P < 0.05, 0.01), suggesting enhanced absorption but reduced total absorption. Only corylin showed no significant difference in any pharmacokinetic parameter. Conclusion The osteoporotic pathological state significantly alters the in vivo disposition of most active components in Psoraleae Fructus. In clinical practice, when using Psoraleae Fructus for osteoporosis treatment, patient disease status should be fully considered, and individualized dosing guided by therapeutic drug monitoring may be necessary to ensure safety and efficacy.

R285.5

国家自然科学基金资助项目（81673826）