建立了测定大鼠血浆中益母草碱(1) 及其葡萄糖醛酸结合物(2) 的LC-MS/MS 方法。考察了大鼠单次和连续28 d灌胃给予低、中、高剂量1(200、600 和2 000 mg/kg) 后1 和2 在体内的暴露水平，绘制药- 时曲线并计算毒代动力学参数。单剂量试验表明，低、中、高剂量组1 的AUC 分别为(1.946±0.908)、(7.002±2.759) 和(26.408±11.491)μmol·L-1·h，1 在大鼠体内消除行为符合线性动力学模型。多剂量试验表明，低、中、高剂量组1 的AUC 分别为(2.987±1.089)、(9.083±
3.140) 和(20.178±7.484)μmol·L-1·h。长期大剂量灌胃给予1，1 和2 均未见在大鼠体内明显蓄积，且试验过程中未见大鼠有明显的毒性反应。

A LC-MS/MS method for determination of leonurine (1) and its metabolite leonurine-O-glucuronide (2) in rat plasma was established. After single- or multiple-dose (once daily for 28 d) ig administration of 1 at low, middle and high doses, the exposure levels of 1 and 2 in rats were investigated. The concentration-time curves of 1 and 2 were drawn and the toxicokinetic parameters were calculated. The AUC of 1 for single-dose ig administration of 200, 600, 2 000 mg/kg were (1.946±0.908), (7.002±2.759) and (26.408±11.491)μmol·L-1·h, respectively. The results suggested that the elimination behavior of 1 in rats accorded with linear dynamic model. The AUC of 1 for multipledose ig administration were (2.987±1.089), (9.083±3.140) and (20.178±7.484)μmol·L-1·h, respectively. No significant accumulation was observed after successive large dose ig administration of 1 in rats. During the experiment there was no significant toxicity in rats.