Simultaneous determination of caffeic acid and its major pharmacologically active metabolites in rat plasma by LC‐MS/MS and its application in pharmacokinetic study

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Abstract
A simple, sensitive and selective high‐performance liquid chromatography electrospray ionization tandem mass spectrometry (LC‐MS/MS) method was developed for simultaneous determination and pharmacokinetic study of caffeic acid (CA) and its active metabolites. The separation with isocratic elution used a mobile phase composed of methanol and water (containing 0.1% formic acid) at a flow rate of 0.2 mL/min. The detection of target compounds was done in selected reaction monitoring (SRM) mode. The SRM detection was operated in the negative electrospray ionization mode using the transitions m/z 179 ([M − H]−) → 135 for CA, m/z 193 ([M − H]−) → 134.8 for ferulic acid and isoferulic acid and m/z 153 ([M − H]−) → 108 for protocatechuic acid. The method was linear for all analytes over the investigated range with all correlation coefficients 0.9931. The lower limits of quantification were 5.0 ng/mL for analytes. The intra‐ and inter‐day precisions (relative standard deviation) were n = 6). The developed method was applied to study the pharmacokinetics of CA and its major active metabolites in rat plasma after oral and intravenous administration of CA. Copyright © 2014 John Wiley & Sons, Ltd.
Funding Information
  • the National Key Special Project of Science and Technology for Innovation Drugs of China (2013zx09402202)

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