Quantification of homoegonol in rat plasma using liquid chromatography-tandem mass spectrometry and its pharmacokinetics application = 랫트 플라스마에서의 호모에고놀 정량

Abstract

Homoegonol is a biologically active neolignan isolated from Styrax species with cytotoxic, antimicrobial, anti-inflammatory and anti-asthma activities. For the quantification of homoegonol in rat plasma, a selective and sensitive liquid chromatography-tandem mass spectrometric method was developed and validated for the first time using protein precipitation with methanol as a sample clean-up procedure. The analytes were separated in an Atlantis dC18 column using a gradient elution of methanol and 0.1% formic acid, and mass-to-charge ratios were determined in selective reaction monitoring mode using tandem mass spectrometry with m/z 343.12>296.97 for homoegonol and m/z 517.30>282.90 for udenafil (internal standard). The standard curve was linear over the concentration ranges of 1-500ng/mL using a 30μL rat plasma sample. The coefficient of variation and relative error for intra- and inter-assay at four quality control levels were 3.9-10.0 and -3.3-2.7%, respectively. The overall recovery of homoegonol from rat plasma using protein precipitation was 99.7±7.7%. The pharmacokinetics parameters of homoegonol were dose-independent after both intravenous (1, 2.5 and 5mg/kg doses) and oral (5, 10 and 20mg/kg doses) administration in male Sprague-Dawley rats.