title: Simultaneous multi-component quantitation of Chinese herbal injection Yin-zhi-huang in rat plasma by using a single-tube extraction procedure for mass spectrometry-based pharmacokinetic measurement.
abstract: Ying-zhi-huang injection (YZH-I) is an injectable multi-herbal prescription derived from the ancient Chinese remedy "Yin-chen-hao-tang", which is widely used in the clinic for the treatment of jaundice and chronic liver diseases. To date, little information is available on the pharmacokinetic properties of this poly-herbal formulation. Herein, we reported a simple, rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantitative multiple reaction monitoring (MRM) of eight major ingredients of YZH-I (including baicalin, baicalein, wogonoside, geniposide, geniposidic acid, chlorogenic acid, neochlorogenic acid, and caffeic acid) in rat plasma. A fast single-tube multi-impurity precipitation extraction ("SMIPE") procedure was introduced for straightforward plasma preparation, based on one-pot deproteinization precipitation with acidified methanol extraction and in-situ multifunction impurity removal by a solid sorbent mixture (anh. magnesium sulfate plus octadecylsilane). Particularly, the addition of ascorbic acid in methanol (10 mg/mL) was found to exhibit a pronounced protective effect and significantly increase extraction effectiveness of the herbal phenolic components. Some pretreatment variables (protein precipitating solvent, acidifying agent and sorbent) were optimized with acceptable matrix effect (-18 to 7.7%), extraction recovery (65-88%) and process efficiency (62-91%) for the SMIPE-based LC-MRM multi-analyte quantitation using matrix-matched calibration (5-1000 ng/mL) without using internal standard. Mean accuracies were obtained in the range of 83-114% at three different fortification levels, with intra- and inter-day variations within 13%. This validated method was successfully applied to the simultaneous measurement and pharmacokinetic investigation of the chemical constituents in rats following an intravenous administration of YZH-I.
authors.affiliation: Key Laboratory of Phytochemical R&D of Hunan Province; Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Technology Center of Hunan Entry-Exit Inspection and Quarantine Bureau of China, Changsha 410004, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Central South University, 172 Tongzipo Road, Changsha 410013, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Phytochemical R&D of Hunan Province; Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081, China. Electronic address: binnguo@126.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
authors.affiliation: Key Laboratory of Phytochemical R&D of Hunan Province; Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Phytochemical R&D of Hunan Province; Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Key Laboratory of Phytochemical R&D of Hunan Province; Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Ye
authors.affiliation: Technology Center of Hunan Entry-Exit Inspection and Quarantine Bureau of China, Changsha 410004, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.affiliation: Key Laboratory of Phytochemical R&D of Hunan Province; Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D002934:Cinnamates / Q000097:blood / Q000493:pharmacokinetics; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D039823:Iridoids / Q000097:blood / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002934:Cinnamates; D004365:Drugs, Chinese Herbal; D039823:Iridoids; C070600:yin zhi huang
keywords: Multi-component quantitation; Multiple reaction monitoring; Pharmacokinetics; Protein precipitation; Single-tube extraction; Yin-zhi-huang formula