Honokiol is a bioactive component isolated from the medicinal herbs Magnolia officinalis and Magnolia grandiflora that has antioxidative, anti-inflammatory, antithrombotic, and antitumor activities. The inhibitory potentials of honokiol on eight major human cytochrome P450 (CYP) enzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4, and four UDP-glucuronosyltransferases (UGTs) 1A1, 1A4, 1A9, and 2B7 in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. Honokiol strongly inhibited CYP1A2-mediated phenacetin O-deethylation, CYP2C8-mediated amodiaquine N-deethylation, CYP2C9-mediated diclofenac 4-hydroxylation, CYP2C19-mediated [S]-mephenytoin 4-hydroxylation, and UGT1A9-mediated propofol glucuronidation with K i values of 1.2, 4.9, 0.54, 0.57, and 0.3 μM, respectively. Honokiol also moderately inhibited CYP2B6-mediated bupropion hydroxylation and CYP2D6-mediated bufuralol 1'-hydroxylation with K i values of 17.5 and 12.0 μM, respectively. These in vitro results indicate that honokiol has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP1A2, CYP2C8, CYP2C9, CYP2C19, and UGT1A9.

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 - 500 ng/mL using a 30 μL 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 5 mg/kg doses) and oral (5, 10 and 20 mg/kg doses) administration in male Sprague-Dawley rats.

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