Planta Med
DOI: 10.1055/s-0043-111895
Original Paper
Georg Thieme Verlag KG Stuttgart · New York

Oral Administration of (S)-Allyl-l-Cysteine and Aged Garlic Extract to Rats: Determination of Metabolites and Their Pharmacokinetics

Taehoon Park1, Ju-Hee Oh2, Joo Hyun Lee2, Sang Cheol Park1, Young Pyo Jang1, 3, Young-Joo Lee1, 2
  • 1Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea
  • 2Division of Biopharmaceutics, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea
  • 3Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea
Further Information

Publication History

received 18 November 2016
revised 28 April 2017

accepted 16 May 2017

Publication Date:
30 May 2017 (eFirst)

Abstract

(S)-Allyl-l-cysteine is the major bioactive compound in garlic. (S)-Allyl-l-cysteine is metabolized to (S)-allyl-l-cysteine sulfoxide, N-acetyl-(S)-allyl-l-cysteine, and N-acetyl-(S)-allyl-l-cysteine sulfoxide after oral administration. An accurate LC-MS/MS method was developed and validated for the simultaneous quantification of (S)-allyl-l-cysteine and its metabolites in rat plasma, and the feasibility of using it in pharmacokinetic studies was tested. The analytes were quantified by multiple reaction monitoring using an atmospheric pressure ionization mass spectrometer. Because significant quantitative interference was observed between (S)-allyl-l-cysteine and N-acetyl-(S)-allyl-l-cysteine as a result of the decomposition of N-acetyl-(S)-allyl-l-cysteine at the detector source, chromatographic separation was required to discriminate (S)-allyl-l-cysteine and its metabolites on a reversed-phase C18 analytical column with a gradient mobile phase consisting of 0.1% formic acid and acetonitrile. The calibration curves of (S)-allyl-l-cysteine, (S)-allyl-l-cysteine sulfoxide, N-acetyl-(S)-allyl-l-cysteine, and N-acetyl-(S)-allyl-l-cysteine sulfoxide were linear over each concentration range, and the lower limits of quantification were 0.1 µg/mL [(S)-allyl-l-cysteine and N-acetyl-(S)-allyl-l-cysteine] and 0.25 µg/mL [(S)-allyl-l-cysteine sulfoxide and N-acetyl-(S)-allyl-l-cysteine sulfoxide]. Acceptable intraday and inter-day precisions and accuracies were obtained at three concentration levels. The method satisfied the regulatory requirements for matrix effects, recovery, and stability. The validated LC-MS/MS method was successfully used to determine the concentration of (S)-allyl-l-cysteine and its metabolites in rat plasma samples after the administration of (S)-allyl-l-cysteine or aged garlic extract.