title: A UPLC-MS/MS method for simultaneous determination of danshensu, protocatechuic aldehyde, rosmarinic acid, and ligustrazine in rat plasma, and its application to pharmacokinetic studies of Shenxiong glucose injection in rats.
abstract: A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of the four major active ingredients, danshensu, protocatechuic aldehyde, rosmarinic acid, and ligustrazine, in the traditional Chinese medicine Shenxiong glucose injection in rat plasma. Acidified and alkalized plasma samples were extracted using ethyl acetate, and separated on a Waters C18 column (2.1mm×50mm, 1.7μm) by using a gradient mobile phase system of acetonitrile-water containing 0.1% formic acid and luteoloside as an internal standard. Electrospray ionization in the positive-ion mode and multiple reaction monitoring were used to identify and quantitate the active components. All calibration curves showed good linearity (r>0.994) over the concentration range, with a lower limit of quantification (LLOQ) between 0.02 and 0.21μg/mL. The precision of the in vivo study was evaluated by intra- and inter-day assays, and the percentage of relative standard deviation was within 15%. Moreover, satisfactory extraction efficiency was obtained (between 83.94 and 117.81%) by liquid-liquid extraction. The validated method was successfully applied in a pharmacokinetic study in rats after intravenous administration of Shenxiong glucose injection. The results showed that the four bioactive ingredients in Shenxiong glucose injection have linear pharmacokinetic properties in rats after intravenous injection within the administered dose range and partially different ones compared to single ingredient.
authors.affiliation: Provincial Key Laboratory of Pharmaceutics in Guizhou Province, School of Pharmacy, Guiyang Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Provincial Key Laboratory of Pharmaceutics in Guizhou Province, School of Pharmacy, Guiyang Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, People's Republic of China.
authors.forename: Zipeng
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Provincial Key Laboratory of Pharmaceutics in Guizhou Province, School of Pharmacy, Guiyang Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Provincial Key Laboratory of Pharmaceutics in Guizhou Province, School of Pharmacy, Guiyang Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, People's Republic of China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Provincial Key Laboratory of Pharmaceutics in Guizhou Province, School of Pharmacy, Guiyang Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, People's Republic of China. Electronic address: mailofhy@126.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Provincial Key Laboratory of Pharmaceutics in Guizhou Province, School of Pharmacy, Guiyang Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Provincial Key Laboratory of Pharmaceutics in Guizhou Province, School of Pharmacy, Guiyang Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, People's Republic of China.
authors.forename: Yanyu
authors.initials: Y
authors.lastname: Lan
authors.affiliation: Provincial Key Laboratory of Pharmaceutics in Guizhou Province, School of Pharmacy, Guiyang Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, People's Republic of China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Wang
authors.affiliation: Provincial Key Laboratory of Pharmaceutics in Guizhou Province, School of Pharmacy, Guiyang Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, People's Republic of China. Electronic address: gywyl@gmc.edu.cn.
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001547:Benzaldehydes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002396:Catechols / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002934:Cinnamates / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D053630:Depsides / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D007275:Injections, Intravenous; D007773:Lactates / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D011719:Pyrazines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods; D000097123:Rosmarinic Acid
chemical_list: D001547:Benzaldehydes; D002396:Catechols; D002934:Cinnamates; D053630:Depsides; D004365:Drugs, Chinese Herbal; D007773:Lactates; D011719:Pyrazines; D000097123:Rosmarinic Acid; C035055:3,4-dihydroxyphenyllactic acid; C005581:protocatechualdehyde; C017953:tetramethylpyrazine
keywords: Danshensu; Ligustrazine; Pharmacokinetic; Shenxiong glucose injection; UPLC–MS/MS