title: Development of an LC-MS/MS method for determining the pharmacokinetics of clonidine following oral administration of Zhenju antihypertensive compound.
abstract: Zhenju antihypertensive compound (ZJAHC) is a combined Chinese-Western medicine formula including clonidine (CLO), hydrochlorothiazide (HCT), rutin, Chrysanthemum indicum extract and pearl powder. Compared with CLO preparations, ZJAHC shows improved activities and decreased adverse effects. It is believed that the side effects of CLO are caused by its high peak plasma concentration. Hence, study of the influence of ZJAHC on the pharmacokinetic behaviors of clonidine seems essential. In present study, the plasma concentrations of CLO were determined with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The MS/MS transitions monitored for clonidine and internal standard were 230.2 → 213.1 and 152.2 → 110.2, respectively. The analyte was quantified in a single run within 3 min. The pharmacokinetic study showed that the area under the plasma concentration-time curve of CLO in ZJAHC (60 µg/kg CLO) was similar to that of CLO-HCT-high (120 µg/kg CLO) but the peak concentration was much lower than that in CLO-HCT-high. ZJAHC could enhance the bioavailability without greatly increasing peak concentration of clonidine. This comprehensive effect of enhancing the bioavailability and avoiding the high peak plasma concentration for CLO might mainly result from the co-contribution of Western medicine and traditional Chinese medicine (TCM), while the effect of TCM was stronger than that of Western medicine.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, 201203, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, 201203, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Heilongjiang University of Chinese Medicine, Haerbin, Heilongjiang Province, 150040, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, 201203, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, 201203, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Shen
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Heilongjiang University of Chinese Medicine, Haerbin, Heilongjiang Province, 150040, China.
authors.forename: Yongji
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, 201203, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, 201203, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods*; D003000:Clonidine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D016014:Linear Models; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000959:Antihypertensive Agents; D004365:Drugs, Chinese Herbal; D003000:Clonidine
keywords: LC-MS/MS; TCM; Zhenju antihypertensive compound; clonidine; pharmacokinetics