Structural Elucidation of in vivo and in vitro Metabolites of Epiberberine in Rat and Its Liver and Intestines by Liquid Chromatography-Tandem Mass Spectrometry

The in vivo and in vitro metabolism of epiberberine was investigated using a highly specific and sensitive liquid chromatography–mass spectrometry (LC–MS/MS) method. In vivo samples including rat urine, feces, and plasma samples were collected individually after ingestion of 35 mg/kg epiberberine to healthy rats. In vitro samples were prepared by incubating epiberberine with homogenized liver and intestinal flora of rats, respectively. As a result, at least 17, 3 and 5 metabolites were found in rat urine, feces, and plasma, respectively. Additionally, 1 and 3 metabolites were found in the rat intestinal flora and homogenized liver incubation mixtures, respectively.     

Characterization of ginsenoside compound K metabolites in rat urine and feces by ultra‐performance liquid chromatography with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry

Ginsenoside compound K (CK) is an active metabolite of ginsenoside and has been shown to have ameliorative property in various diseases. However, the detailed in vivo metabolism of this compound has rarely been reported. In the present study, a method using liquid chromatography quadrupole time‐of‐flight tandem mass spectrometry together with multiple data processing techniques, including extracted ion chromatogram, multiple mass defect filter and MS/MS scanning, was developed to detect and characterize the metabolites of CK in rat urine and feces. After oral administration of CK at a dose of 50 mg/kg, urine and feces were collected for a period of time and subjected to a series of pretreatment. A total of 12 metabolites were tentatively or conclusively identified, comprising 11 phase I metabolites and a phase II metabolite. Metabolic pathways of CK has been proposed, including oxidation, deglycosylation, deglycosylation with sequential oxidation and dehydrogenation and deglycosylation with sequential glucuronidation. Relative quantitative analyses suggested that deglycosylation was the main metabolic pathway. The result could offer insights for better understanding of the mechanism of its pharmacological activities.     

In vivo metabolism study of ginsenoside Re in rat using high-performance liquid chromatography coupled with tandem mass spectrometry

Ginsenoside Re is one of the major the bioactive triterpene saponins in ginseng root, a well-known adaptogen in traditional Chinese medicine. It is believed that the lead compound may be further developed into a promising new drug for preventing hypertension and cardiovascular disease. To better understand the pharmacological activities of the component, an investigation of its in vivo metabolism was necessary. In the present study, a high-performance liquid chromatography coupled with electrospray ionization and quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-TOF-MS/MS) has been applied to discover and identify the metabolites of ginsenoside Re in rat urine following intravenous and oral administration of the component, respectively. The rat urine samples were collected and pretreated through C₁₈ solid-phase extraction cartridges prior to analysis. Negative electrospray ionization mass spectrometry was used to discern ginsenoside Re and its possible metabolites in urine samples. The metabolites were identified and tentatively characterized by means of comparing molecular mass, retention time, and fragmentation pattern of the analytes with those of the parent compound, ginsenoside Re. As a result, eleven and nine metabolites together with Re were detected and identified in rat urine collected after intravenous and oral administration, respectively. A possible metabolic pathway of ginsenoside Re was also investigated and proposed. Oxidation and deglycosylation were found to be the major metabolic processes of the constituent in rat.      

Quantification of ginsenosides Rh4 and Rk3 in rat plasma by liquid chromatography‐tandem mass spectrometry: Application to a pre‐clinical pharmacokinetic study

Ginsenoside Rh4 (Rh4) and ginsenoside Rk3 (Rk3) are two active substances isolated from the processed Panax species. To further explore their potential medicinal application, a reliable liquid chromatography‐tandem mass spectrometry method (LC/MS/MS) was developed and validated for the quantification of Rh4 and Rk3 in rat plasma. Multiple ion monitoring and multiple reaction monitoring experiments were performed in negative ionization mode. This LC/MS/MS method had good selectivity, sensitivity (lower limit of quantification = 10 ng/mL), precision (intra‐ and inter‐day relative standard deviation ≤ 10.1) and accuracy (analytical recovery within 100 ± 10%). The pharmacokinetic profiles of Rh4 and Rk3 were subsequently assessed in Sprague–Dawley rats. Similar to many other ginsenosides, the oral bioavailability of Rh4 and Rk3 was unfavorable, and Rh4 and Rk3 did not have any measurable plasma exposure after oral administration (20 mg/kg). Fortunately, upon intravenous administration (5 mg/kg), both Rh4 and Rk3 possessed abundant plasma exposure, moderate clearance (Cl = 50.2 ± 7.7 and 23.8 ± 1.4 mL·min^?1·kg^?1, respectively) and terminal elimination half‐life (t_{1/2 λZ} = 157.2 ± 65.2 and 99.5 ± 37.8 min, respectively). As Rh4 and Rk3 displayed favorable intravenous pharmacokinetic profiles, further exploration on their medicinal application is warranted. Copyright © 2012 John Wiley & Sons, Ltd.     

High performance liquid chromatography-mass spectrometry analysis for rat metabolism and pharmacokinetic studies of lithospermic acid B from danshen

Metabolism and pharmacokinetic studies on rat were conducted for lithospermic acid B, one of the components from Radix Salviae Miltiorrhizae (danshen) that shows many bioactivities. Liquid chromatography-electrospray ionization mass spectrometry method was applied for the determination of lithospermic acid B and its metabolites in samples from in vitro and in vivo metabolism studies. Rat plasma samples collected after intravenous administration were analyzed for obtaining pharmacokinetic data of lithospermic acid B. Four O-methylated metabolites, namely one monomethyl-, two dimethyl- and one trimethyl-lithospermic acid B, were detected when lithospermic acid B was incubated in rat hepatic cytosol. These four metabolites were also detected in rat bile, plasma and feces samples after intravenous administration of lithospermic acid B. The in vitro and in vivo results indicate that the methylation is the main metabolic pathway of lithospermic acid B. The danshen component and its methylated metabolites were excreted to rat bile and feces.     

LC/MS/MS for identification of in vivo and in vitro metabolites of jatrorrhizine

The in vivo and in vitro metabolism of jatrorrhizine has been investigated using a specific and sensitive LC/MS/MS method. In vivo samples including rat feces, urine and plasma collected separately after dosing healthy rats with jatrorrhizine (34 mg/kg) orally, along with in vitro samples prepared by incubating jatrorrhizine with rat intestinal flora and liver microsome, respectively, were purified using a C(18) solid-phase extraction cartridge. The purified samples were then separated with a reversed-phase C(18) column with methanol-formic acid aqueous solution (70:30, v/v, pH3.5) as mobile phase and detected by on-line MS/MS. The structural elucidation of the metabolites was performed by comparing their molecular weights and product ions with those of the parent drug. As a result, seven new metabolites were found in rat urine, 13 metabolites were detected in rat feces, 11 metabolites were detected in rat plasma, 17 metabolites were identified in intestinal flora incubation solution and nine metabolites were detected in liver microsome incubation solution. The main biotransformation reactions of jatrorrhizine were the hydroxylation reaction, the methylation reaction, the demethylation reaction and the dehydrogenation reaction of parent drug and its relative metabolites. All the results were reported for the first time, except for some of the metabolites in rat urine.     

The biotransformation of oleuropein in rats

A highly sensitive and specific LC‐MS/MS method was developed to investigate the in vivo bio‐transformation of oleuropein in rat. Rat feces and urine samples collected after oral administration were determined by liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the negative‐ion mode. The assay procedure involves a simple liquid–liquid extraction of parent oleuropein and the metabolite from rat feces and urine with ethyl acetate. Chromatographic separation was operated with 0.1% formic acid aqueous and methanol in gradient program at a flow rate of 0.50 mL/min on an RP‐C₁₈ column with a total run time of 31 min. This method was successfully applied to simultaneous determination of oleuropein and its metabolites in rat feces and urine. De‐glucosylation, hydrolysis, oxygenation and methylation were found to comprise the major metabolic pathway of oleuropein in rat gastrointestinal tract and three metabolites were absorbed into the blood circulatory system within 24 h after oral administration. Copyright © 2013 John Wiley & Sons, Ltd.     

快速高分辨液相色谱-质谱联用技术分析2型糖尿病大鼠口服四君子汤的药代动力学

研究四君子汤在2型糖尿病大鼠体内的药代动力学。 将四君子汤水提物以18 g/kg给正常大鼠和2型糖尿病大鼠灌胃,分别在不同时间点取尿液和粪便,检测其成分及代谢产物的含量;比较正常大鼠和2型糖尿病大鼠的药代动力学参数。 采用快速高分辨液相色谱-质谱联用技术对人参皂苷Rc、甘草甜素及其脱糖代谢物进行表征。 结果表明,四君子汤中人参皂苷Rc和甘草甜素在2型糖尿病大鼠体内的累计排泄率均高于正常大鼠,大部分人参皂苷通过尿液排出体外、粪便代谢为稀有人参皂苷;大部分甘草甜素在尿液和粪便中转化为甘草次酸,2型糖尿病大鼠与正常大鼠人参皂苷Rc和甘草甜素的药代动力学参数存在明显差异。 初步总结了四君子汤在体内的药代动力学机制和代谢途径。本分析方法具有高度自动化,灵敏性和准确性,这将有助于四君子汤的临床研究的不断发展。     

In vivo metabolism study of vaccarin in rat using HPLC‐LTQ‐MSn

In order to illustrate the main biotransformation pathways of vaccarin in vivo, metabolites of vaccarin in rats were identified using a specific and sensitive high‐performance liquid chromatography–electrospray ionization linear ion trap mass spectrometry (LTQ XL?) method. The rats were administered a single dose (200 mg/kg) of vaccarin by oral gavage. By comparing their changes in molecular masses (ΔM), retention times and spectral patterns with those of the parent drug, the parent compound and six metabolites were found in rat urine after oral administration of vaccarin. The parent compound and five metabolites were detected in rat plasma. In heart, liver and kidney samples, respectively, one, four and three metabolites were identified, in addition to the parent compound. Three metabolites, but no trace of parent drug, were found in the rat feces. This is the first systematic metabolism study of vaccarin in vivo. The biotransformation pathways of vaccarin involved methylation, hydroxylation, glycosylation and deglycosylation. Copyright © 2012 John Wiley & Sons, Ltd.     

High-performance liquid chromatographic determination of xanthohumol in rat plasma, urine, and fecal samples

Xanthohumol (XN) is the major prenylated flavonoid in hop plants and as such a constituent of beer. Pharmacological studies have shown that XN possesses marked antioxidant and antiproliferative effects. In order to study the resorption and metabolism of this compound, reversed-phase high-performance liquid chromatography is used for the determination of XN in rat plasma, urine, and feces. In session one, rats receive either oral or intravenous (iv) administration (20 mg/kg body weight) of XN. In session two, rats receive oral administration of 50, 100, 200, 400, and 500 mg/kg body weight XN for bioavailability studies at various dose levels. Plasma, urine, and feces are collected at varying time points and assayed for their XN content. Plasma levels of XN fell rapidly within 60 min after iv administration; no XN is detected in plasma after oral administration in either session. XN and its metabolites are excreted mainly in feces within 24 h of administration. The method is a reliable tool for performing studies of XN in different biological material.     

Simultaneous determination of imperatorin and its metabolites in vitro and in vivo by a GC‐MS method: application to a bioavailability and protein binding ability study in rat plasma

In this study, a simple and sensitive gas chromatography–mass spectrometry method was developed for the study of bioavailability and protein binding and the metabolism of imperatorin in rat. The results showed that the pharmacokinetics of imperatorin after intravenous and oral administration in rats exhibited linear characteristics. The absolute bioavailability of imperatorin was calculated as ~3.85, ~33.51 and ~34.76% for 6.25, 12.5 and 25 mg/kg, respectively. The low bioavailability of imperatorin may be attributed to the poor absorption or extensive metabolism. The phase I metabolites of imperatorin formed in vitro by rat liver microsomes were studied, and two metabolites were isolated and identified as xanthotoxol and heraclenin. Following oral administration of imperatorin, one metabolite (heraclenin) was detected in rat plasma, and two potential metabolites (xanthotoxol and heraclenin) were detected in rat urine. However, none of potential metabolites was detected in rat feces and bile. The results showed that the metabolites of imperatorin were excreted by kidney, and heraclenin was associated with an active component. Demethylation and oxygenization were the main metabolic pathways. In vitro plasma protein binding of imperatorin was 90.1 and 92.6% for the spiked rat plasma concentrations of 1.0 and 50.0 µg/mL, respectively, indicating that imperatorin showed slow distribution into the intra‐ and extracellular space. Copyright © 2013 John Wiley & Sons, Ltd.     

Identification and structural characterization of in vivo metabolites of ketorolac using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI‐MS/MS)

In vivo metabolites of ketorolac (KTC) have been identified and characterized by using liquid chromatography positive ion electrospray ionization high resolution tandem mass spectrometry (LC/ESI‐HR‐MS/MS) in combination with online hydrogen/deuterium exchange (HDX) experiments. To identify in vivo metabolites, blood urine and feces samples were collected after oral administration of KTC to Sprague–Dawley rats. The samples were prepared using an optimized sample preparation approach involving protein precipitation and freeze liquid separation followed by solid‐phase extraction and then subjected to LC/HR‐MS/MS analysis. A total of 12 metabolites have been identified in urine samples including hydroxy and glucuronide metabolites, which are also observed in plasma samples. In feces, only O‐sulfate metabolite and unchanged KTC are observed. The structures of metabolites were elucidated using LC‐MS/MS and MSⁿ experiments combined with accurate mass measurements. Online HDX experiments have been used to support the structural characterization of drug metabolites. The main phase I metabolites of KTC are hydroxylated and decarbonylated metabolites, which undergo subsequent phase II glucuronidation pathways. Copyright © 2012 John Wiley & Sons, Ltd.     

Metabolic profiling of quercetin in rats using ultra‐performance liquid chromatography/quadrupole‐time‐of‐flight mass spectrometry

Quercetin, a kind of major flavonoid found in many traditional chinese medicines, is an effective substance for treatments such as lowering blood lipids. However, the studies on quercetin have been mainly focused on its pharmacological effect; the treatment of diseases on a material basis, particularly the metabolites derived from quercetin in vivo , has not been evaluated. In this study, we determined the levels, distributions and types of quercetin's metabolites in plasma, urine, feces and bile of rats after a single oral administration of quercetin at a dose of 80 mg/kg, using ultra‐performance liquid chromatography/quadrupole‐time‐of‐flight mass spectrometry (UPLC‐Q‐TOF/MS). A total of 36 metabolites of quercetin were identified, including 11 metabolites in plasma, 34 metabolites in urine, 12 metabolites in feces and 21 metabolites in bile. The results showed that phase I metabolites were reduction metabolites and phase II metabolites mainly included glucuronidation, sulfation and methylation metabolites. These results provide important information on the metabolism of quercetin, which will be helpful for its further development and utilization.     

Metabolite profiling of ginsenoside Rg1 after oral administration in rat

The goal of this study is to investigate the biotransformation of ginsenoside Rg₁ in vivo. A highly sensitive and specific LC‐MS/MS method was developed and used for metabolite identification in rat feces and urine after oral administration of ginsenoside Rg₁. Four metabolites of Rg₁ were detected in rat feces and three metabolites of Rg₁ were detected in rat urine. Deglycosylation and oxygenation were found to be the major metabolic pathways of ginsenoside Rg₁ after oral administration in rat. Except for the reported metabolites Rh₁ and protopanaxatriol, mono‐oxygenated Rg₁ and mono‐oxygenated protopanaxatriol were detected for the first time after oral administration of Rg₁. The in vivo metabolite profiling of ginsenoside Rg₁ in rat was proposed. Viewed collectively, Rg₁ was metabolized to mono‐oxygenated Rg₁, Rh₁, protopanaxatriol and the secondary metabolite mono‐oxygenated protopanaxatriol in rat. Copyright © 2014 John Wiley & Sons, Ltd.     

In vivo metabolic investigation of silodosin using UHPLC–QTOF–MS/MS and in silico toxicological screening of its metabolites

Silodosin (SLD) is a novel α1‐adrenoceptor antagonist which has shown promising clinical efficacy and safety in patients with benign prostatic hyperplasia (BPH). However, lack of information about metabolism of SLD prompted us to investigate metabolic fate of SLD in rats. To identify in vivo metabolites of SLD, urine, feces and plasma were collected from Sprague–Dawley rats after its oral administration. The samples were prepared using an optimized sample preparation approach involving protein precipitation followed by solid‐phase extraction and then subjected to LC/HR‐MS/MS analysis. A total of 13 phase I and six phase II metabolites of SLD have been identified in rat urine which includes hydroxylated, N‐dealkylated, dehydrogenated, oxidative, glucosylated, glucuronide and N‐sulphated metabolites, which are also observed in feces. In plasma, only dehydrogenated, N‐dealkylated and unchanged SLD are observed. The structure elucidation of metabolites was done by fragmentation in MS/MS in combination with HRMS data. The potential toxicity profile of SLD and its metabolites were predicted using TOPKAT software and most of the metabolites were proposed to show a certain degree of skin sensitization and occular irritancy. Copyright © 2016 John Wiley & Sons, Ltd.     

Stereoselective determination of ginsenosides Rg3 and Rh2 epimers in rat plasma by LC‐MS/MS: Application to a pharmacokinetic study

We developed and validated an accurate and sensitive LC–MS/MS method for the simultaneous quantitation of ginsenoside Rg3 and Rh2 epimers (R‐Rg3, S‐Rg3, R‐Rh2, and S‐Rh2) in rat plasma. Analytes were extracted from 0.1 mL aliquots of rat plasma by liquid–liquid extraction, using 2 mL of ethyl acetate. In this assay, dioscin (500 ng/mL) was used as an internal standard. Chromatographic separation was conducted using an Acclaim RSLC C₁₈ column (150 × 2.1 mm, 2.2 μm) at 40°C, with a gradient mobile phase consisting of 0.1% formic acid in distilled water and in acetonitrile, a flow rate of 0.35 mL/min, and a total run time of 20 min. Detection and quantification were performed using a mass spectrometer in selected reaction‐monitoring mode with negative electrospray ionization at m/z 783.4 → 161.1 for R‐Rg3 and S‐Rg3, m/z 621.3 → 161.1 for R‐Rh2 and S‐Rh2, and m/z 867.2 → 761.5 for the internal standard. For R‐Rg3 and S‐Rg3, the lower limit of quantification was 5 ng/mL, with a linear range up to 500 ng/mL; for R‐Rh2 and S‐Rh2, the lower limit of quantification was 150 ng/mL, with a linear range up to 6000 ng/mL. The coefficient of variation for assay precision was less than 10.5%, with an accuracy of 86.4–112%. No relevant cross‐talk or matrix effect was observed. The method was successfully applied to a pharmacokinetic study after oral administration of 400 mg/kg and 2000 mg/kg of BST204, a fermented ginseng extract, to rats. We found that the S epimers exhibited significantly higher plasma concentrations and area under curve values for both Rg3 and Rh2. This is the first report on the separation and simultaneous quantification of R‐Rg3, S‐Rg3, R‐Rh2, and S‐Rh2 in rat plasma by LC‐MS/MS. The method should be useful in the clinical use of ginseng or its derivatives.     

Liquid chromatography-electrospray ionization ion trap mass spectrometry for analysis of in vivo and in vitro metabolites of scopolamine in rats

In vivo and in vitro metabolism of scopolamine is investigated using a highly specific and sensitive liquid chromatography-mass spectrometry (LC-MSn) method. Feces, urine, and plasma samples are collected individually after ingestion of 55 mg/kg scopolamine by healthy rats. Rat feces and urine samples are cleaned up by a liquid-liquid extraction and a solid-phase extraction procedure (C18 cartridges), respectively. Methanol is added to rat plasma samples to precipitate plasma proteins. Scopolamine is incubated with homogenized liver and intestinal flora of rats in vitro, respectively. The metabolites in the incubating solution are extracted with ethyl acetate. Then these pretreated samples are injected into a reversed-phase C18 column with mobile phase of methanol-ammonium acetate (2 mM, adjusted to pH 3.5 with formic acid) (70:30, v/v) and detected by an on-line MSn system. Identification and structural elucidation of the metabolites are performed by comparing their changes in molecular masses (DeltaM), retention-times and full scan MSn spectra with those of the parent drug. The results reveal that at least 8 metabolites (norscopine, scopine, tropic acid, aponorscopolamine, aposcopolamine, norscopolamine, hydroxyscopolamine, and hydroxyscopolamine N-oxide) and the parent drug exist in feces after administering 55 mg/kg scopolamine to healthy rats. Three new metabolites (tetrahydroxyscopolamine, trihydroxy-methoxyscopolamine, and dihydroxy-dimethoxyscopolamine) are identified in rat urine. Seven metabolites (norscopine, scopine, tropic acid, aponorscopolamine, aposcopolamine, norscopolamine, and hydroxyscopolamine) and the parent drug are detected in rat plasma. Only 1 hydrolyzed metabolite (scopine) is found in the rat intestinal flora incubation mixture, and 2 metabolites (aposcopolamine and norscopolamine) are identified in the homogenized liver incubation mixture.     

超高效液相色谱-四极杆-飞行时间质谱检测和鉴定猪尿中氯丙那林的主要代谢产物

采用超高效液相色谱-四极杆-飞行时间质谱(UPLC/Q-TOF MS)检测和鉴定了猪尿中氯丙那林的主要代谢产物,并讨论了氯丙那林在猪体内的主要代谢途径。按10 mg/kg(b. w.)的剂量口服灌食氯丙那林,分别采集给药前及给药后的猪尿液样品。采用UPLC/Q-TOF MS对样品进行分析,并应用质量亏损过滤和离子色谱峰提取等数据处理技术,在给药后24 h内的猪尿中检测和鉴定了9种氯丙那林的代谢产物,其中,Ⅰ相代谢产物2种,Ⅱ相代谢产物7种。然后,根据氯丙那林原形和代谢产物的碎片离子特征,对代谢产物的结构进行鉴定。最后,根据所鉴定的代谢产物,推测氯丙那林在猪体内的代谢途径包括苯环羟基化、β -羟基和仲氨基的葡萄糖醛酸轭合、羟基化后的葡萄糖醛酸和硫酸轭合等。研究结果表明,羟基化氯丙那林及其轭合产物的相对含量大于60%,明显高于氯丙那林原形及其轭合产物,是尿液中的主要代谢产物。本研究将为确定氯丙那林在动物体内的残留标示物及加强对氯丙那林非法使用的监控提供科学依据。     

Systematic characterization of the metabolites of echinacoside and acteoside from Cistanche tubulosa in rat plasma,bile, urine and feces based on UPLC‐ESI‐Q‐TOF‐MS

Echinacoside (ECH) and acteoside (ACT), as the most and major active components of Cistanche tubulosa, were reported to possess cardioactive, neuroprotective and hepatocyte protective effects, as well as antibacterial, antioxidative effects. Recently, more studies have focused on their pharmacological activities. However, their metabolic profiles in vivo have not been sufficiently investigated. This study proposes an approach for rapidly identifying the complicated and unpredictable metabolites of ECH and ACT in rat plasma, bile, urine and feces, and systematically and comprehensively revealing their major metabolic pathways, based on powerful ultra‐high performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry. Plasma, bile, urine and feces were collected from rats after a single 200 mg/kg oral dose. A total of 49 metabolites were detected in rat biological samples. Through analyzing metabolites in bile samples, it was found that ECH and ACT were subjected to a marked hepatic first‐pass effect in liver. Copyright © 2016 John Wiley & Sons, Ltd.     

In vitro and in vivo identification of metabolites of magnoflorine by LC LTQ‐Orbitrap MS and its potential pharmacokinetic interaction in Coptidis Rhizoma decoction in rat

Magnoflorine, an important aporphine alkaloid in Coptidis Rhizoma, is increasingly attracting research attention because of its pharmacological activities. The in vivo and in vitro metabolism of magnoflorine was investigated by LC LTQ‐Orbitrap MS. In vivo samples including rat urine, feces, plasma and bile were collected separately after both oral (50 mg kg^?1) and intravenous administration (10 mg kg^?1) of magnoflorine, along with in vitro samples prepared by incubating magnoflorine with rat intestinal flora and liver microsome. As a result, 12 metabolites were found in biological samples. Phase I metabolites were identified in all biological samples, while phase II metabolites were mainly detected in urine, plasma and bile. In a pharmacokinetic study, rats were not only dosed with magnoflorine via oral (15, 30 and 60 mg kg^?1) and intravenous administration (10 mg kg^?1) but also dosed with Coptidis Rhizoma decoction (equivalent to 30 mg kg^?1 of magnoflorine) by intragastric administration to investigate the interaction of magnoflorine with the rest of compounds in Coptidis Rhizoma. Studies showed that magnoflorine possessed lower bioavailability and faster absorption and elimination. However, pharmacokinetic parameters altered significantly (p < 0.05) when magnoflorine was administered in Coptidis Rhizoma decoction. Oral gavage of Coptidis Rhizoma decoction decreased the absorption and elimination rates of magnoflorine, which revealed that there existed pharmacokinetic interactions between magnoflorine and the rest of ingredients in Coptidis Rhizoma. Copyright © 2015 John Wiley & Sons, Ltd.