Bhattarai Sushila, Tran Van H, Duke Colin C
Faculty of Pharmacy, University of Sydney, NSW 2006, Australia.
J Pharm Biomed Anal. 2007 Nov 30;45(4):648-53. doi: 10.1016/j.jpba.2007.07.006. Epub 2007 Jul 10.
The degradation kinetics of [6]-gingerol and [6]-shogaol were investigated in simulated gastric (pH 1) and intestinal (pH 7.4) fluids at 37 degrees C. Degradation products were quantitatively determined by HPLC (Lichrospher 60 RP select B column, 5 microm, 125 mm x 4 mm; mobile phase: methanol-water-acetic acid (60:39:1 v/v); flow rate: 0.6 ml/min; detection UV: 280 nm). In simulated gastric fluid (SGF) [6]-gingerol and [6]-shogaol underwent first-order reversible dehydration and hydration reactions to form [6]-shogaol and [6]-gingerol, respectively. The degradation was catalyzed by hydrogen ions and reached equilibrium at approximately 200 h. In simulated intestinal fluid (SIF) both [6]-gingerol and [6]-shogaol showed insignificant interconversion between one another. Addition of amino acids glycine, 3-amino propionic acid (beta-alanine) and gamma-amino butyric acid (GABA), and ammonium acetate at a range of concentrations of 0.05-0.5mM had no effect on the rate of degradation of [6]-shogaol in SGF and 0.1M HCl solution. However, at exceedingly high concentration (0.5M) of ammonium acetate and glycine, significant amounts of [6]-shogaol ammonia and glycine adducts were detected. The degradation profile of [6]-gingerol and [6]-shogaol under simulated physiological conditions reported in this study will provide insight into the stability of these compounds when administered orally.
在37℃的模拟胃液(pH 1)和肠液(pH 7.4)中研究了[6]-姜酚和[6]-姜烯酚的降解动力学。降解产物通过高效液相色谱法(Lichrospher 60 RP select B柱,5μm,125 mm×4 mm;流动相:甲醇-水-乙酸(60:39:1 v/v);流速:0.6 ml/min;紫外检测:280 nm)进行定量测定。在模拟胃液(SGF)中,[6]-姜酚和[6]-姜烯酚分别发生一级可逆脱水和水合反应,形成[6]-姜烯酚和[6]-姜酚。降解由氢离子催化,约200 h达到平衡。在模拟肠液(SIF)中,[6]-姜酚和[6]-姜烯酚之间的相互转化不明显。添加浓度范围为0.05 - 0.5 mM的氨基酸甘氨酸、3-氨基丙酸(β-丙氨酸)和γ-氨基丁酸(GABA)以及乙酸铵对SGF和0.1 M HCl溶液中[6]-姜烯酚的降解速率没有影响。然而,在乙酸铵和甘氨酸浓度极高(0.5 M)时,检测到大量的[6]-姜烯酚氨和甘氨酸加合物。本研究报道的模拟生理条件下[6]-姜酚和[6]-姜烯酚的降解情况将有助于深入了解这些化合物口服给药时的稳定性。