Structural elucidation of in vivo and in vitro metabolites of anisodine by liquid chromatography-tandem mass spectrometry

Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESIMSn) was employed to investigate the in vivo and in vitro metabolism of anisodine. Feces, urine and plasma samples were collected after ingestion of 20 mg anisodine to healthy rats. Feces and urine samples were cleaned up by liquid-liquid extraction and solid-phase extraction procedures (C18 cartridges), respectively. Methanol was added to plasma samples to precipitate plasma proteins. Anisodine was incubated with homogenized liver and intestinal flora of rats in vitro, respectively, followed by extraction with ethyl acetate. LC-MSn was used for the separation and identification of the metabolites using C18 column with mobile phase of methanol/0.01% triethylamine solution (2 mM, adjusted to pH 3.5 with formic acid) (60:40, v/v). The results revealed that five metabolites (norscopine, scopine, alpha-hydroxytropic acid, noranisodine and hydroxyanisodine) and the parent drug existed in feces. Three new metabolites (dimethoxyanisodine, tetrahydroxyanisodine and trihydroxy-methoxyanisodine) were identified in urine. Four metabolites (norscopine, scopine, hydroxyanisodine and anisodine N-oxide) and the parent drug were detected in plasma. Two hydrolyzed metabolites (scopine and alpha-hydroxytropic acid) were found in rat intestinal flora incubation mixture, and two metabolites (aponoranisodine and anisodine N-oxide) were identified in homogenized liver incubation mixture.     

Polymethoxylated flavones metabolites in rat plasma after the consumption of Fructus aurantii extract: analysis by liquid chromatography/electrospray ion trap mass spectrometry

A LC with full scan MS(n) method was developed in order to investigate the in vivo absorption and biotransformation of polymethoxylated flavones (PMFs) by analysis of plasma samples from rats after ingestion of Fructus aurantii extract. Four parent compounds and six metabolites with intact flavonoid structures were tentatively identified. The metabolites were either glucuronides of parent compounds or glucuronides of demethylated products of parent compounds.     

In vivo metabolites of S-(2-benzothiazolyl)-L-cysteine as markers of in vivo cysteine conjugate beta-lyase and thiol glucuronosyl transferase activities

Cysteine conjugate beta-lyases (beta-lyase), enzymes that are present in mammalian liver, kidneys, and intestinal microflora, were exploited recently for site-selective delivery of 6-mercaptopurine to the kidneys. In this study, in vivo beta-lyase activity was assessed using S-(2-benzothiazolyl)-L-cysteine (BTC). 2-Mercaptobenzothiazole and 2-mercaptobenzothiazole S-glucuronic acid were major metabolites of BTC in rat liver, kidney, plasma, and urine. Total metabolite concentrations in liver, kidney, or plasma at 30 min were similar and were higher than that detected at 3 hr; metabolites were mostly in the glucuronide form. The portions of metabolites excreted in urine at 8 and 24 hr were nearly 93 and 99% of that excreted at 40 hr, respectively. Pretreatment of rats with aminooxyacetic acid did not alter kidney, liver, plasma, or urinary metabolite concentrations. The portion of the BTC dose excreted as metabolites at 24 hr was independent of the BTC dose (100-400 mumol/kg), age (5-12 weeks), or sex of the rats. The rates of in vitro BTC metabolism by guinea pig hepatic and renal beta-lyases were slower than those of rats, but the portion of the BTC dose recovered as metabolites in guinea pig urine at 24 hr was nearly 60%, which was nearly 2-fold higher than that recovered in urine of rats, mice, or hamsters. The amounts of total metabolites excreted into urine by mice or hamsters were similar, but the portion of metabolites that was in the glucuronide form in hamster urine was higher than that in mouse urine.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Spermatogenic Effect of Yacon Extract and Its Constituents and Their Inhibition Effect of Testosterone Metabolism

We screened the pharmacological effects of a 50% ethanol extract of Yacon tubers and leaves on spermatogenesis in rats. As a result, we found that Yacon tuber extracts increased sperm number and serum testosterone level in rats. It has been reported that the crude extract of Yacon tubers and leaves contain phenolic acids, such as, chlorogenic acid, ferulic acid and caffeic acid by HPLC/MS analysis. We were interested in the contributions made by phenolic acid, particularly chlorogenic acid of Yacon tuber extract to the spermatogenic activity. After administering Yacon tuber extract or chlorogenic acid to rats for 5 weeks, numbers of sperm in epididymis were increased by 34% and 20%, respectively. We also administered ferulic acid, which has been reported to be a metabolite of chlorogenic acid and a constituent of Yacon tuber extract to investigate its spermatogenic activity in rats. Yacon tuber extract and ferulic acid increased sperm numbers by 43% and 37%, respectively. And, Yacon tuber extract, and chlorogenic acid showed significantly inhibition effect of testoeterone degradation in rat liver homogenate. We considered that the spermatogenic effect of Yacon tuber extract might be related to phenolic compounds and their inhibitory effect of testosterone degradation. Yacon showed the possibility as ameliorable agents of infertility by sperm deficiency and late onset hypogonadism syndrome with low level of testosterone.     

Identification of in‐vivo and in‐vitro metabolites of palmatine by liquid chromatography–tandem mass spectrometry

Objectives Despite its important therapeutic value, the metabolism of palmatine is not yet clear. Our objective was to investigate its in‐vivo and in‐vitro metabolism. Methods Liquid chromatography–tandem electrospray ionization mass spectrometry (LC‐ESI/MSⁿ) was employed in this work. In‐vivo samples, including faeces, urine and plasma of rats, were collected after oral administration of palmatine (20 mg/kg) to rats. In‐vitro samples were prepared by incubating palmatine with intestinal flora and liver microsome of rats, respectively. All the samples were purified via a C₁₈ solid‐phase extraction procedure, then chromatographically separated by a reverse‐phase C₁₈ column with methanol–formic acid aqueous solution (pH 3.5, 70: 30 v/v) as mobile phase, and detected by an on‐line MSⁿ detector. The structure of each metabolite was elucidated by comparing its molecular weight, retention time and full‐scan MSⁿ spectra with those of the parent drug. Key findings The results revealed that 12 metabolites were present in rat faeces, 13 metabolites in rat urine, 7 metabolites in rat plasma, 10 metabolites in rat intestinal flora and 9 metabolites in rat liver microsomes. Except for six of the metabolites in rat urine, the other in‐vivo and in‐vitro metabolites were reported for the first time. Conclusions Seven new metabolites of palmatine (tri‐hydroxyl palmatine, di‐demethoxyl palmatine, tri‐demethyl palmatine, mono‐demethoxyl dehydrogen palmatine, di‐demethoxyl dehydrogen palmatine, mono‐demethyl dehydrogen palmatine, tri‐demethyl dehydrogen palmatine) were reported in this work.     

Comparison of dietary triacylglycerol oil and diacylglycerol oil in protein kinase C activation.

The objective of the present study was to compare the effects of dietary diacylglycerol (DAG) oil with triacylglycerol (TAG) oil with a similar fatty acid composition (fatty acid chain range: C14-C22, C18 fatty acid chain: >90%) on protein kinase C (PKC) activation and on 1,2-DAG levels. Using male Wistar rats, no differences in cytosolic and membrane PKC activities in the lingual, esophageal, gastric, small intestinal, cecal, proximal colonic, and distal colonic mucosa were found between the 5% DAG and TAG oil groups, or between the 23% DAG and TAG oil groups after 1 month of feeding. The 1,2-DAG levels in the cecum and colon contents and in the feces and serum in male Wistar rats after a diet containing either 10% DAG or TAG oil feeding were similar between the groups. Moreover, exposure of Caco-2 cells to DAG and TAG oils had no effect on PKC activity in the membrane fraction, but 1,2-dioctanoyl glycerol composed of short-chain fatty acids (C8) did, suggesting the absence of an influence on PKC activity in DAG and TAG oils composed of long-chain fatty acids. In summary, the effects of DAG oil ingestion on PKC activity in the digestive tract and lingual mucosa, and on 1,2-DAG levels in the cecum and colon contents and in the feces and serum were similar to those observed for TAG oil ingestion.     

Isolation, identification and antiviral activities of metabolites of calycosin-7-O-β-D-glucopyranoside

In vivo and in vitro metabolites of calycosin-7-O-β-d-glucopyranoside in rats were identified using a specific and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MSⁿ) method. The parent compound and twelve metabolites were found in rat urine after oral administration of calycosin-7-O-β-d-glucopyranoside. The parent compound and six metabolites were detected in rat plasma. In heart, liver, spleen, lung and kidney samples, respectively, six, eight, seven, nine and nine metabolites were identified, in addition to the parent compound. Three metabolites, but no trace of parent drug, were found in the rat intestinal flora incubation mixture and feces, which demonstrated cleavage of the glycosidic bond of the parent compound in intestines. The main phase I metabolic pathways of calycosin-7-O-β-d-glucopyranoside in rats were deglycosylation, dehydroxylation and demethylation reactions; phase II metabolism included sulfation, methylation, glucuronidation and glycosylation (probably). Furthermore, two metabolites commonly found in rat urine, plasma and tissues were isolated from feces and characterized by NMR. The antiviral activities of the metabolite calycosin against coxsackie virus B₃ (CVB₃) and human immunodeficiency virus (HIV) were remarkably stronger than those of calycosin-7-O-β-d-glucopyranoside.     

Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors

Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is important to identify biomarkers that positively correspond with brain Mn-accumulation. The objective of this study was to identify Mn-induced alterations in plasma, liver, and brain metabolites using liquid/gas chromatography-time of flight-mass spectrometry metabolomic analyses; and to monitor corresponding Mn-induced behavior changes. Weanling Sprague-Dawley rats had access to deionized drinking water either Mn-free or containing 1 g Mn/L for 6 weeks. Behaviors were monitored during the sixth week for a continuous 24 h period while in a home cage environment using video surveillance. Mn-exposure significantly increased liver, plasma, and brain Mn concentrations compared to control, specifically targeting the globus pallidus (GP). Mn significantly altered 98 metabolites in the brain, liver, and plasma; notably shifting cholesterol and fatty acid metabolism in the brain (increased oleic and palmitic acid; 12.57 and 15.48 fold change (FC), respectively), and liver (increased oleic acid, 14.51 FC; decreased hydroxybutyric acid, − 14.29 FC). Additionally, Mn-altered plasma metabolites homogentisic acid, chenodeoxycholic acid, and aspartic acid correlated significantly with GP and striatal Mn. Total distance traveled was significantly increased and positively correlated with Mn-exposure, while nocturnal stereotypic and exploratory behaviors were reduced with Mn-exposure and performed largely during the light cycle compared to unexposed rats. These data provide putative biomarkers for Mn-neurotoxicity and suggest that Mn disrupts the circadian cycle in rats.     

淫羊藿苷在大鼠体内的代谢

目的：为阐明淫羊藿苷在体内的作用形式,对淫羊藿苷的代谢产物及活性进行研究。方法：将淫羊藿苷给大鼠ig后,分析、分离并鉴定了其在小肠、尿、胆汁中的主要代谢产物。结果：在小肠及尿中鉴定有淫羊藿次苷II(icariside II)及淫羊藿素(icaritin),胆汁中有淫羊藿素3-O-α-L-鼠李吡喃糖基-7-O-β-D-葡萄吡喃糖醛酸苷(icaritin 3-O-α-L-rhamnopyranosyl-7-O-β-D-glucopyranuronoside)和淫羊藿次苷II,并对淫羊藿苷在大鼠体内主要代谢途径进行了探讨。结论：淫羊藿苷在吸收之前已发生代谢,在体内主要是以其代谢产物的形式存在。     

Structure elucidation of in vivo and in vitro metabolites of mangiferin

The in vivo and in vitro metabolism of mangiferin was systematically investigated. Urine, plasma, feces, contents of intestinal tract and various organs were collected after oral administration of mangiferin to healthy rats at a dose of 200mg/kg body weight. For comparison, mangiferin was also incubated in vitro with intestinal flora of rats. With the aid of a specific and sensitive liquid chromatography coupled with electrospray ionization tandem hybrid ion trap mass spectrometry (LC-ESI-IT-MS(n)), a total of thirty-three metabolites of mangiferin were detected and their structures were tentatively elucidated on the basis of the characteristics of their precursor ions, product ions and chromatographic retention times. The biotransformation pathways of mangiferin involved deglycosylation, dehydroxylation, methylation, glycosylation, glucuronidation and sulfation.     

Identification of the absorbed components and metabolites in rat plasma after oral administration of Rhizoma Chuanxiong decoction by HPLC-ESI-MS/MS

An HPLC-ESI-MS/MS method was established to identify the absorbed components and metabolites in rat plasma after oral administration of Rhizoma Chuanxiong decoction (RCD), a well-known traditional Chinese medicine. By comparing the extracted ion chromatograms (EICs) obtained from dosed rat plasma, blank rat plasma and RCD, a total of 25 compounds were detected in dosed rat plasma. Among them, 13 compounds were absorbed into rat plasma in prototype and identified as ferulic acid, senkyunolide J, senkyunolide I, senkyunolide D or 4,7-dihydroxy-3-butylphthalide, senkyunolide F, senkyunolide M, senkyunolide Q, senkyunolide A, E-butylidenephthalide, E-ligustilide, neocnidilide, Z-ligustilide, levistolide A, according to the retention times, UV, MS, MS/MS spectra. In addition, 12 conjugated metabolites including 6 senkyunolide I-related metabolites, 4 senkyunolide J-related metabolites and 2 butylidenephthalide-related metabolites were also detected and identified by comparing their MS, MS/MS spectra with that of corresponding original components. Conjugated with glutathione, cysteine, glucuronic acid and sulphuric acid were the main metabolic reactions of phthalides. Finally the in vivo metabolic pathways of chemical constituents of Chuanxiong in rat plasma were proposed in this study.     

Characterization of metabolites of worenine in rat biological samples using liquid chromatography–tandem mass spectrometry

The in vivo and in vitro metabolites of worenine in rat were identified or characterized using a specific and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. In vivo samples including rat urine, feces, and plasma samples were collected after ingestion of 25 mg/kg worenine to healthy rats. The in vivo and in vitro samples were cleaned up by a solid-phase extraction procedure (C18 cartridges) and a liquid–liquid extraction procedure, respectively. Then these pretreated samples were injected into a reversed-phase C18 column with mobile phase of methanol–ammonium acetate (2 mM, adjusted to pH 3.5 with formic acid) (60:40, v/v) and detected by an on-line MS/MS system. As a result, at least twenty-seven metabolites and the parent medicine were found in rat urine after ingestion of worenine. Seven metabolites and the parent medicine were identified or characterized in rat feces. Three metabolites and the parent medicine were detected in rat plasma. One metabolite was found in the rat intestinal flora incubation mixture, and three metabolites were characterized in the homogenized liver incubation mixture. The main phase I metabolism of worenine in rat was dehydrogenization, hydrogenation, hydroxylation, and demethylene reactions, and that of phase II was sulfation and glucuronidation.     

Comparison of in vitro preparations for semi-quantitative prediction of in vivo drug metabolism.

Various in vitro preparations were compared with respect to their ability to mimic in vivo metabolism. For this purpose, S9-liver homogenate, microsomes, cryopreserved hepatocytes, cryopreserved liver slices and fresh liver, lung, kidney, and intestinal slices were incubated with three drugs in development, which are metabolized in vivo by a wide range of biotransformation pathways. Metabolites were identified and quantified with liquid chromatography-mass spectometry/UV from the in vitro incubations and compared with metabolite patterns in feces, urine, and bile of dosed rats. In vitro systems with intact liver cells produced the same metabolites as the rat in vivo and are a valuable tool to study drug metabolism. Phase I metabolites were almost all conjugated in intact cells, whereas S9-homogenate only conjugated by sulfation and N-acetylation. Microsomes and S9-homogenate are useful to study phase I metabolism but not for the prediction of in vivo metabolism. Extra-hepatic organ slices did not form any metabolites that were not produced by liver cells, but the relative amounts of the various metabolites differed considerably. Small intestinal slices were more active than liver slices in the formation of the N-glucuronide of compound C, which is the major metabolite in vivo. When the relative contribution of liver and small intestinal slices to the metabolism of this compound was taken into account, it appeared that the in vivo metabolite pattern could be well predicted. Results indicate that for adequate prediction of in vivo metabolism, fresh or cryopreserved liver slices or hepatocytes in combination with slices of the small intestines should be used.     

The effect of haem biosynthesis inhibitors and inducers on intestinal iron absorption and liver haem biosynthetic enzyme activities

The relation between haem biosynthesis and intestinal iron absorption is not well understood, we therefore investigated the effect of compounds that alter haem metabolism on duodenal iron absorption. CD1 mice were treated with either an inhibitor (succinyl acetone (SA)) or stimulator (2-allyl-2-isopropylacetamide (AIA)) of haem biosynthesis. 5-Aminolaevulinic acid (ALA) dehydratase and urinary ALA and porphobilinogen (PBG) levels, were determined. Intestinal iron absorption was assayed with in vivo and in vitro techniques. Liver hepcidin (Hamp1) and duodenal iron transporter mRNA levels were measured using RT-PCR. AIA caused increased hepatic ALA synthase (1.6-fold) and ALA dehydratase (1.4-fold, both p<0.005) activities and increased urinary ALA and PBG excretion (2.1- and 1.4-fold, p<0.005, p<0.05, respectively). In vivo intestinal iron absorption was reduced to 49% of control (p<0.005). Mice treated with SA showed decreased urinary ALA and PBG levels (75 and 55% control, both p<0.005) and reductions in both ALA synthase and ALA dehydratase activities (77 and 56% control, p<0.05, p<0.005, respectively) in the liver. Liver and duodenal haem and cytochrome oxidase levels were not significantly decreased. Iron absorption was enhanced (1.26-fold, p<0.05) and hepatic Hamp1 mRNA was reduced (53% of control, p<0.05). In vitro duodenal iron uptake after mice were injected with SA also demonstrated an increase in Fe(III) reduction and uptake (1.27- and 1.41-fold, p<0.01 respectively). Simultaneous injections of SA and ALA blocked the enhancing effect on iron absorption seen with SA alone. We conclude that alterations in haem biosynthesis can influence iron absorption and in particular, the intermediate ALA seems to be an inhibitor of iron absorption.     

In vitro and in vivo determination of piperacillin metabolism in humans.

Piperacillin metabolism and biliary excretion are different between humans and preclinical species. In the present study, piperacillin metabolites were characterized in bile and urine of healthy humans and compared with metabolites formed in vitro. Volunteers were administered 2 g of piperacillin IV; blood, urine, and duodenal aspirates (obtained via a custom-made oroenteric catheter) were collected. The metabolism of piperacillin in humans also was investigated in vitro using pooled human liver microsomes and sandwich-cultured human hepatocytes. Piperacillin and metabolites were estimated by high-performance liquid chromatography with tandem mass spectrometry detection. Piperacillin, desethylpiperacillin, and desethylpiperacillin glucuronide were detected in bile, urine, and human liver microsomal incubates. Similar to the in vivo results, desethylpiperacillin was formed and excreted into bile canaliculi of sandwich-cultured human hepatocytes. This is the first report of glucuronidation of desethylpiperacillin in vitro or in vivo. The clinical method employed in this study to determine biliary clearance of drugs also facilitates bile collection as soon as bile is excreted from the gallbladder, thereby minimizing the exposure of labile metabolites to the intestinal environment. This study exemplifies how a combination of in vitro and in vivo tools can aid in the identification of metabolites unique to the human species.     

Hexachlorobenzene stimulates uroporphyria in low affinity AHR mice without increasing CYP1A2

Adult female Fisher 344 rats received drinking water containing 0, 4, 40, 100, or 200 parts per million of dimethylarsinic acid or 100 parts per million of arsenate for 14 days. Urine was collected during the last 24 h of exposure. Tissues were then taken for analysis of dimethylated and trimethylated arsenicals; urines were analyzed for these arsenicals and their thiolated derivatives. In dimethylarsinic acid-treated rats, highest concentrations of dimethylated arsenic were found in blood. In lung, liver, and kidney, concentrations of dimethylated arsenic exceeded those of trimethylated species; in urinary bladder and urine, trimethylated arsenic predominated. Dimethylthioarsinic acid and trimethylarsine sulfide were present in urine of dimethylarsinic acid-treated rats. Concentrations of dimethylated arsenicals were similar in most tissues of dimethylarsinic acid- and arsenate-treated rats, including urinary bladder which is the target for dimethylarsinic acid-induced carcinogenesis in the rat. Mean concentration of dimethylated arsenic was significantly higher (P<0.05) in urine of dimethylarsinic acid-treated rats than in arsenate-treated rats, suggesting a difference between treatment groups in the flux of dimethylated arsenic through urinary bladder. Concentrations of trimethylated arsenic concentrations were consistently higher in dimethylarsinic acid-treated rats than in arsenate-treated rats; these differences were significant (P<0.05) in liver, urinary bladder, and urine. Concentrations of dimethylthioarsinic acid and trimethylarsine sulfide were higher in urine from dimethylarsinic acid-treated rats than from arsenate-treated rats. Dimethylarsinic acid is extensively metabolized in the rat, yielding significant concentrations of trimethylated species and of thiolated derivatives. One or more of these metabolites could be the species causing alterations of cellular function that lead to tumors in the urinary bladder.     

Function and expression of the proton-coupled amino acid transporter PAT1 along the rat gastrointestinal tract: implications for intestinal absorption of gaboxadol

BACKGROUND AND PURPOSE Intestinal absorption via membrane transporters may determine the pharmacokinetics of drug compounds. The hypothesis is that oral absorption of gaboxadol (4,5,6,7-tetrahydroisoxazolo [5,4-c] pyridine-3-ol) in rats occurs via the proton-coupled amino acid transporter, rPAT1 (encoded by the gene rSlc36a1). Consequently, we aimed to elucidate the in vivo role of rPAT1 in the absorption of gaboxadol from various intestinal segments obtained from Sprague-Dawley rats. EXPERIMENTAL APPROACH The absorption of gaboxadol was investigated following its administration into four different intestinal segments. The intestinal expression of rSlc36a1 mRNA was measured by quantitative real-time PCR. Furthermore, the hPAT1-/rPAT1-mediated transport of gaboxadol or L-proline was studied in hPAT1-expressing Xenopus laevis oocytes, Caco-2 cell monolayers and excised segments of the rat intestine. KEY RESULTS The absorption fraction of gaboxadol was high (81.3-91.3%) following its administration into the stomach, duodenum and jejunum, but low (4.2%) after administration into the colon. The pharmacokinetics of gaboxadol were modified by the co-administration of L-tryptophan (an hPAT1 inhibitor) and L-proline (an hPAT1 substrate). The in vitro carrier-mediated uptake rate of L-proline in the excised intestinal segments was highest in the mid jejunum and lowest in the colon. The in vitro uptake and the in vivo absorption correlated with the expression of rSlc36a1 mRNA along the rat intestine. CONCLUSIONS AND IMPLICATIONS These results suggest that PAT1 mediates the intestinal absorption of gaboxadol and therefore determines its oral bioavailability. This has implications for the in vivo role of PAT1 and may have an influence on the design of pharmaceutical formulations of PAT1 substrates.     

黄山药总皂苷肠内菌代谢及代谢产物吸收的研究

目的 :本文离体和整体观察人和大鼠肠内菌对黄山药总皂苷(DX)的代谢作用及整体给予DX后吸收入血的有效成分。方法 :用薄层色谱(TLC)及电喷雾质谱(ESI -MS)法检测粪中DX及其代谢产物。整体给予大鼠灌服DX900mg/kg ,于给药后不同时间采集尿及血清样品 ,用ESI -MS检测吸收入血成分。结果 :DX容易被人和大鼠消化道菌群代谢 ,随着代谢时间的延长 ,出现了各种甾体皂苷的降解产物及终产物薯蓣皂苷元 (Dio)。整体实验表明 ,在大鼠血及尿中均发现分子量为415 3的代谢产物 ,经ESI -MS二级质谱分析 ,上述分子量的化合物为Dio。结论 :DX可被人和大鼠肠内菌代谢 ,DX经口服后Dio被吸收入血。     

黄山药总皂甙肠内菌代谢及代谢产物吸收的研究

目的：本离体和整体观察人和大鼠肠内菌对黄山药总皂苷（DX）的代谢作用及整体给予DX后吸收入血的有效成分，方法：用薄层色谱（TLC）及电喷雾质谱（ESI－MS）法检测粪中DX及其代谢产物。整体给予大鼠灌服DX900mg/kg，于给药后不同时间采集尿及血清样品，用ESI－MS检测吸收入血成分。结果：DX容易被人和大鼠消化道菌群代谢，随着代谢时间的延长，出现了各种甾体皂苷的降解产物及终产物薯蓣皂苷元（Dio)。整体实验表明，在大鼠血及尿中均发现分子量为415．3的代谢产物，经ESIMS二级质谱分析，上述分子量的化合物为Dio。结论：DX可被人和大鼠肠内菌代谢，DX经口服后Dio被吸收入血。