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Simultaneous determination of nine constituents by validated UFLC-MS/MS in the plasma of cough variant asthma rats and its application to pharmacokinetic study after oral administration of Huanglong cough oral liquid.

Abstract
Huanglong cough oral liquid (HL), an important traditional Chinese medicine prescription for treating pediatric cough variant asthma (CVA) in Nanjing hospital of traditional Chinese medicine for many years. In this study, a selective, accurate and sensitive ultra fast liquid chromatography extreme resolution coupled with mass spectrometer (UFLC-MS/MS) method was established and validated for the simultaneous determination of nine constituents including morusin, ephedrine, praeruptorin A, praeruptorin B, luteolin, rosmarinic acid, quercetin, amygdalin, caffeic acid in CVA rat plasma sensitized and challenged with ovalbumin and cinnamaldehyde. Plasma samples were prepared by protein precipitation with four-fold amount of methanol. UFLC separation was performed on a Thermo Scientific AcclaimTM RSLC 120 C18 column (2.1 mm × 100 mm, 2.2 μm) with mobile phase containing methanol and 0.1% formic acid-water by gradient elution in 8.1 min at total flow of 0.3 mL/min. The determination of target compounds in plasma was operated by multiple reaction monitoring (MRM) mode with positive and negative electrospray ionization (ESI) source. The correlation coefficients (r) of all compounds were from 0.9930 to 0.9994 in the linear range. Lower limit of quantification (LLOQ, ng/mL) was 0.81, 2.01, 2.11, 1.17, 1.04, 0.89, 0.67, 1.45 and 0.59 for morusin, ephedrine, praeruptorin A, praeruptorin B, luteolin, rosmarinic acid, quercetin, amygdalin and caffeic acid, respectively. Intra- and inter-day accuracy and precision, extraction recovery, matrix effect, carryover effect, dilution integrity, and stability were within the limits specified. The established method was effectively applied to a pharmacokinetic study of the nine compounds in CVA rat plasma following oral administration HL exact (7.5, 15, 30 g/kg).
AuthorsZheng Liu, Xiaoqian Wu, Zhenyang Si, Desong Kong, Dongwei Yang, Fuqiong Zhou, Zhujun Wang
JournalJournal of pharmaceutical and biomedical analysis (J Pharm Biomed Anal) Vol. 193 Pg. 113726 (Jan 30 2021) ISSN: 1873-264X [Electronic] England
PMID33171336 (Publication Type: Journal Article)
CopyrightCopyright © 2020 Elsevier B.V. All rights reserved.
Chemical References
  • Drugs, Chinese Herbal
Topics
  • Administration, Oral
  • Animals
  • Asthma (drug therapy)
  • Child
  • Chromatography, High Pressure Liquid
  • Cough (drug therapy)
  • Drugs, Chinese Herbal
  • Humans
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Tandem Mass Spectrometry

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