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

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 967; pp. 245 - 254
• Main Authors: Zeng, Le, Wang, Meiling, Yuan, Yu, Guo, Bin, Zhou, Jing, Tan, Zhen, Ye, Meiling, Ding, Li, Chen, Bo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.09.2014
• Subjects: Animals; ascorbic acid; baicalin; caffeic acid; chlorogenic acid; Chromatography, Liquid - methods; Cinnamates - blood; Cinnamates - pharmacokinetics; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - analysis; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacokinetics; ingredients; intravenous injection; Iridoids - blood; Iridoids - pharmacokinetics; jaundice; Linear Models; liquid chromatography; liver diseases; magnesium sulfate; Male; methanol; monitoring; Multi-component quantitation; Multiple reaction monitoring; Pharmacokinetics; protective effect; Protein precipitation; quantitative analysis; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Single-tube extraction; solvents; tandem mass spectrometry; Tandem Mass Spectrometry - methods; Yin-zhi-huang formula; Protein precipitation; Single-tube extraction; Yin-zhi-huang formula; Multi-component quantitation; Pharmacokinetics; Multiple reaction monitoring
• ISSN: 1570-0232; 1873-376X; 1873-376X
• DOI: 10.1016/j.jchromb.2014.07.037

•A new “SMIPE” procedure developed for straightforward bio-sample preparation.•One-pot multifunction impurity removal for matrix-matched external standard calibration.•Mass spectrometric multiple reaction monitoring of Yin-zhi-huang herbal prescription in vivo.•Simultaneous multi-component pharmacokinetic study of Yin-zhi-huang injection for the first time. 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 (10mg/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 (5–1000ng/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.