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目的:研究20名健康受试者单剂量口服2片酚麻美敏片(每片含对乙酰氨基酚325 mg,盐酸伪麻黄碱30 mg,氢溴酸右美沙芬15 mg,马来酸氯苯那敏2 mg)后氢溴酸右美沙芬及其代谢物O-去甲右美沙芬的人体药代动力学。方法:以盐酸克仑特罗为内标,采用LC-MS/MS法ESI正离子化,选择性反应监测,同时测定人血浆中的氢溴酸右美沙芬及其代谢物O-去甲右美沙芬浓度;并采用β-葡萄糖醛酸酶酶解后测定O-去甲右美沙芬总量浓度,采用DAS 2.0计算药动学参数。结果:测得血浆中游离氢溴酸右美沙芬和O-去甲右美沙芬的主要药代动力学参数分别为Cmax(4.4±4.6),(9.7±5.4)μg.L-1;Tmax(4.2±3.3),(1.8±0.8)h;AUC0-τ(61.0±84.2),(59.4±25.4)h.μg.L-1;t1/2(9.5±2.9),(6.0±2.8)h;MRT0-τ(13.8±5.5),(7.6±2.8)h。酶解后测得O-去甲右美沙芬的主要药代动力学参数为Cmax(536±165)μg.L-1;Tmax(2.1±0.6)h;AUC0-τ(3504±710)h.μg.L-1;t1/2(6.4±2.7)h;MRT0-τ(7.2±2.3)h。结论:建立的LC-MS/MS测定法准确灵敏。健康受试者单剂量口服酚麻美敏片后的血浆中葡萄糖醛酸结合型O-去甲右美沙芬的浓度显著高于游离氢溴酸右美沙芬和O-去甲右美沙芬。
OBJECTIVE: To study the effects of phenylephrine tablet (oral tablet containing acetaminophen 325 mg, pseudoephedrine hydrochloride 30 mg, dextromethorphan hydrobromide 15 mg, chlorpheniramine maleate 2 mg) dextromethorphan hydrobromide and its metabolite O-dextromethorphan in human pharmacokinetics. Methods: Clenbuterol hydrochloride was used as an internal standard. ESI positive ionization and selective reaction monitoring were carried out by LC-MS / MS. Meanwhile, dextromethorphan hydrobromide and its metabolite O-dexamethasone The concentration of dextromethorphan was determined by enzymatic hydrolysis of β-glucuronidase, and the pharmacokinetic parameters were calculated by DAS 2.0. RESULTS: The main pharmacokinetic parameters of free dextromethorphan hydrobromide and o-dextromethorphan in plasma were Cmax (4.4 ± 4.6), (9.7 ± 5.4) μg.L-1 and Tmax ( 4.2 ± 3.3), (1.8 ± 0.8) h; AUC0-τ (61.0 ± 84.2), (59.4 ± 25.4) h.μg.L-1; t1 / 2 MRT0-τ (13.8 ± 5.5), (7.6 ± 2.8) h. The main pharmacokinetic parameters of O-desmethyl dextromethorphan measured after enzymatic hydrolysis were Cmax (536 ± 165) μg.L-1; Tmax (2.1 ± 0.6) h; AUC0-τ (3504 ± 710) h. t1 / 2 (6.4 ± 2.7) h; MRT0-τ (7.2 ± 2.3) h. Conclusion: The established LC-MS / MS assay is accurate and sensitive. The concentration of glucuronide-bound dextromethorphan in plasma after a single oral dose of phenamil in healthy subjects was significantly higher than that of dextromethorphan hydrobromide and o-dextromethorphan.