National TCM Key Lab of Serum Pharmacochemistry, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China; Institute of Natural Medicine, University of Toyama, Toyama, Japan.
J Sep Sci. 2014 Feb;37(3):237-43. doi: 10.1002/jssc.201300898. Epub 2013 Dec 27.
The metabolism of gentiopicroside (GPS) in vivo was studied for the first time by LC-MS following picolinoyl derivatization. Incubation of erythrocentaurin, one of the main in vitro metabolites of GPS by intestinal bacteria, with liver microsome indicated that GPS might be metabolized to a final metabolite 3,4-dihydro-5-(hydroxymethyl)isochroman-1-one (HMIO) in vivo. After hydrolysis with sulfatase, HMIO was successfully detected in rat plasma after oral administration of GPS by LC-MS following picolinoyl derivatization. 4-Methoxyphenyl methanol was used as an internal standard to quantify HMIO in rat plasma. A metabolic pathway of GPS in rats is proposed. The monoterpene compound GPS was found to be metabolized to dihydroisocoumarin, which may be responsible for the pharmacological effect of GPS.
首次通过 LC-MS 结合吡啶甲酰化衍生法研究了龙胆苦苷（GPS）在体内的代谢情况。孵育红景天苷，GPS 由肠道细菌产生的主要体外代谢物之一，与肝微粒体表明 GPS 可能在体内代谢为最终代谢物 3,4-二氢-5-（羟甲基）异苯并呋喃-1-酮（HMIO）。用硫酸酯酶水解后，通过 LC-MS 结合吡啶甲酰化衍生法，成功地检测到 GPS 口服给药后大鼠血浆中的 HMIO。4-甲氧基苯甲醇被用作内标来定量大鼠血浆中的 HMIO。提出了 GPS 在大鼠体内的代谢途径。发现单萜化合物 GPS 被代谢为二氢异香豆素，这可能是 GPS 药理作用的原因。
