Serum pharmacochemistry combined with multiple data processing approach to screen the bioactive components and their metabolites in Mutan Cortex by ultra‐performance liquid chromatography tandem mass spectrometry

Root cortex of Paeonia suffruticosa Andrews (Paeoniaceae), known as Moutan Cortex (MC), is known to have anti‐allergic and anti‐inflammatory properties. However, the constituents absorbed into blood after oral administration of MC remain unknown. A sensitive and rapid method by ultra‐high‐pressure liquid chromatography–electrospray ionization–quadrupole‐time‐of‐flight mass spectrometry (UPLC‐ESI‐Q‐TOF‐MS) technology and the MetaboLynx^TM software combined with multiple data processing approach (Mdpa) was established to investigate the absorbed constituents in rats after oral administration of MC, providing unique high‐throughput capabilities for drug metabolism study. A hyphenated electrospray ionization and quadrupole‐time‐of‐flight analyzer was used for the determination of accurate mass of the fragment ion in negative mode, with excellent MS mass accuracy and enhanced data acquisition. This rapid automated analysis method was successfully applied for screening and identification of the constituents absorbed and metabolized studies of MC after oral administration to rats. A total of 46 peaks were obtained from MC, 41 of which were tentatively characterized. In the VIP‐plot of orthogonal partial least‐squares discriminant analysis, 23 interesting ions in serum samples were extracted, and 16 parent components and seven metabolites were detected in vivo. The integrative serum pharmacochemistry technique, UPLC‐ESI‐Q‐TOF‐MS, and Mdpa method were successfully applied for rapid discovery of multiple components from MC. Copyright © 2013 John Wiley & Sons, Ltd.     

Comparative pharmacokinetic study of the main components of cortex fraxini after oral administration in normal and hyperuricemic rats

Cortex Fraxini is an important traditional Chinese herbal medicine used for the treatment of gout and hyperuricemia. An efficient and rapid ultra‐performance liquid chromatography mass spectrometry method was developed and validated for simultaneous quantitation of six coumarins (aesculin, fraxin, aesculetin, fraxetin, sopoletin and 7‐hydroxycoumarin) in normal and hyperuricemic rats plasma after oral administration of Cortex Fraxini. The method could successfully be applied for pharmacokinetics studies. The pharmacokinetic behavior of six coumarins in normal and hyperuricemia rats plasma was determined. Results showed that, for some of analytes, the pharmacokinetic parameters (AUC_0–t , AUC_0–∞, C _max, T _max and CL ) were significantly different between normal and hyperuricemic rats. The different pharmacokinetic parameters might result from renal impairment or a change of metabolic enzymes in the pathological state. The pharmacokinetic study in pathological state could provide more useful information to guide the clinical use of traditional Chinese herbal medicine.     

Ultra high performance liquid chromatography with synapt high‐definition mass spectrometry and a pattern recognition approach to characterize chemical constituents and rat metabolites after the oral administration of Phellinus igniarius

Phellinus igniarius has antibacterial, antiviral, antioxidative, antitumor, and antimutagenic effects. In this study, an integrative pattern recognition approach using principal component analysis and orthogonal partial least squares discriminant analysis was successfully applied for the rapid analysis of natural compounds in traditional Chinese medicine. An ultra high performance liquid chromatography with synapt high‐definition mass spectrometry method and MassLynx software was used. This method employed gradient elution to rapidly analyze and characterize chemical constituents and metabolites after the oral administration of a P. igniarius ethanol extract. There were 24 peaks within 10 min of the analysis time and 20 of these were identified or tentatively characterized on the basis of their fragmentation behaviors. In the S‐plot of the orthogonal partial least squares discriminant analysis, 27 ions were extracted to make the serum. Among them, nine absorbed the prototype components and 18 metabolites were identified in vivo. Glucuronidation, oxidation, and methylation were the major metabolic reactions. This study is the first systematic analysis and characterization of the chemical constituents and metabolites in an ethanol extract of P. igniarius. This method can be applied to the rapid analysis and characterization of constituents in rat serum after the oral administration of other compounds used in traditional Chinese medicines.     

UPLC–Q‐TOF–MS and UPLC–MS/MS methods for metabolism profiles and pharmacokinetics of major compounds in Xuanmai Ganjie Granules

Xuanmai Ganjie Granules (XMGJ), a widely used Chinese herbal formula in the clinic, is used for treatment of sore throats and coughs. Despite the chemical constituents having been clarifying by our previous studies, both of the metabolism and pharmacokinetic studies of XMGJ are unclear. This study aimed to explore the disposition process of XMGJ in vivo. A sensitive and selective ultra‐high performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry (UPLC–Q‐TOF–MS) method was developed to analyze the absorbed components and metabolites in rat plasma and urine after oral administration of XMGJ. A total of 42 absorbed components, including 16 prototype compounds and 26 metabolites, were identified or tentatively characterized in rat plasma and urine after oral administration of XMGJ. Moreover, the pharmacokinetic studies of five compounds of XMGJ were investigated using ultra‐high liquid chromatography with tandem mass spectrometry method. The results indicated that liquiritin, harpagoside, glycyrrhetic acid, liquiritigenin, formononetin and their metabolites might be the major components involved in the pharmacokinetic and metabolism process of XMGJ. This research showed a comprehensive investigation of XMGJ in vivo, which could provide a meaningful basis for further material basis and pharmacological as well as toxicological research.     

Rapid discovery of absorbed constituents and metabolites in rat plasma after the oral administration of Zi Shen Wan using high‐throughput UHPLC–MS with a multivariate analysis approach

Zi Shen Wan is a typical formula consisting of three herbs, Phellodendri Amurensis Cortex, Rhizoma Anemarrhenae, and Cortex Cinnamomi, and has been widely used for treating prostatitis and infection diseases. However, it lacks in‐depth research of the constituents of Zi Shen Wan in vivo and in vitro. In this work, ultra high performance liquid chromatography coupled with quadrupole‐time‐of‐flight mass spectrometry and MassLynx software was established to characterize the chemical compositions of Zi Shen Wan in vivo and in vitro. In total, 92 peaks were characterized in vitro and 33 peaks were characterized in vivo based on mass spectrometry and tandem mass spectrometry data. Among the 33 compounds characterized in rat plasma, 22 prototype components absorbed in rat serum and 11 metabolites were identified in vivo. This work was fully reports the chemical constituents of traditional Chinese formula of Zi Shen Wan, it demonstrated that ultra high performance liquid chromatography combined with quadrupole time‐of‐flight mass spectrometry coupled to MassLynx software and multivariate data processing approach could be successfully applied for rapid screening and comprehensive analysis of chemical constituents in vitro and prototype components or metabolites in vivo of traditional Chinese medicine.     

Identification of absorbed constituents and in vivo metabolites in rats after oral administration of Physalis alkekengi var. franchetii by ultra‐high‐pressure liquid chromatography quadrupole time‐of‐flight mass spectrometry

The calyces of Physalis alkekengi var. franchetii (Chinese Lantern, JDL) are well‐known as traditional Chinese medicine owing to its various therapeutic effects. However, the bioactive constituents responsible for the pharmacological effects of JDL and their metabolites in vivo are still unclear to date. In this paper, an ultra‐high‐pressure liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (UHPLC/Q‐TOF‐MS/MS) method was established to identify absorbed constituents and in vivo metabolites in rat biological fluids after oral administration of JDL. Based on the proposed strategy, 33 compounds were observed in dosed rat biosamples. Twelve of 33 compounds were indicated as prototype components of JDL, and 21 compounds were predicted to be metabolites of JDL. Finally, the metabolic pathways were proposed, which were glucuronidation, sulfation, methylation and dehydroxylation for flavonoid constituents and sulfonation and hydroxylation for physalin consitituents. This is the first systematic study on the absorbed constituents and metabolic profiling of JDL and will provide a useful template for screening and characterizing the ingredients and metabolites of traditional Chinese medicine.     

Studies on chemical constituents of Flos Puerariae-Semen Hoveniae medicine pair by HPLC and Fourier transform ion cyclotron resonance mass spectrometry

Alcoholic liver disease is currently the most clinically concerning liver disease, which occurs from chronic alcohol abuse. Flos Puerariae and Semen Hoveniae have been used to treat alcohol drinking excessively for thousands of years in China. In this study, the ethanol extract of the medicine pair was qualitatively and quantitatively analyzed by high-performance liquid chromatography and Fourier transform ion cyclotron resonance mass spectrometry. First, the high-performance liquid chromatography fingerprint was established to obtain the overall chromatographic data of its chemical constituents. Next, high-performance liquid chromatography-mass spectrometry was applied to identify its chemical constituents. Then, the characteristic constituents were simultaneously quantified by high-performance liquid chromatography. In addition, the chemical constituents that were absorbed into rat plasma were identified by high-performance liquid chromatography-mass spectrometry. As a result, a total of 48 chemical constituents in the medicine pair were detected and identified in vitro. Meanwhile, the content of seven representative constituents, including dihydromyricetin, glycitin, genistin, tectoridin, glycitein, genistein, and tectorigenin were simultaneously determined. Furthermore, a total of 19 chemical constituents were detected in rat plasma after oral administration. In short, the chemical constituents of the medicine pair were initially investigated in this study, which will lay the foundation for the discovery of its pharmacodynamic substances in further works.     

An effective method for determining the ingredients of Shuanghuanglian formula in blood samples using high‐resolution LC–MS coupled with background subtraction and a multiple data processing approach

Shuanghuanglian formula (SF) is a combination of Flos lonicerae japonicae, Radix scutellariae, and Fructus forsythiae, commonly used to treat viral or bacterial infections. However, the constituents absorbed into the blood after oral administration of SF are difficult to determine and thus remain unclear. Here, we report the application of an accurate background subtraction and multiple data processing approach (Bs‐Mpa) for the comprehensive detection of compounds of SF in vivo. A sensitive and reliable ultra‐performance LC coupled with ESI quadrupole TOF MS (UPLC–ESI‐Q‐TOF‐MS) approach coupled with Bs‐Mpa, which is implemented in the Strip tool from UPLC to remove nonrelated ion signals from accurate mass LC–MS data, was established to characterize the chemical constituents and rat metabolites of SF. In the loading plot of the principal component analysis, 68 ions of interest were extracted from blood samples, among them, 39 absorbed prototype components of SF and 29 metabolites were identified in vivo. It is concluded that the integrative Bs‐Mpa method can be successfully applied for the rapid discovery of multiple components from a traditional Chinese medicine. The above challenge was addressed by using the proposed Bs‐Mpa method and it was particularly suitable for applying to the global characterization of the constituents or metabolites in rat blood after oral administration of other well‐known formulae.     

Rapid identification of chemical composition and metabolites of Pingxiao Capsule in vivo using molecular networking and untargeted data-dependent tandem mass spectrometry

Pingxiao capsule (PXC) is a herbal medicine used for adjuvant therapy in breast cancer. However, the constituents and absorbed components of the formula and their related metabolites have not been elucidated to date. PXC is a typical traditional Chinese medicine formula consisting of Strychnos nux-vomica L., Curcuma wenyujin Y. H., Agrimonia pilosa Ledeb., Toxicodendron vernicifluum, Trogopterus dung, alumen, potassium nitrate (saltpeter) and Citrus aurantium L. In this study, a ultra-high performance liquid chromatography system equipped with high resolution Q-Orbitrap mass spectrometry (MS) and comparative Global Natural Product Social molecular networking together with the Compound Discoverer software were used to identify metabolites of PXC in vitro and in vivo. Based on untargeted data-dependent MS² and data-mining techniques, 89 peaks of alkaloids, flavonoids, organic acid and phenolic compounds were identified in a PXC 70% methanol extract. Furthermore, 15 absorbed prototype compounds and their metabolites were rapidly confirmed in rat blood. Glucuronidation, oxidation, methylation and hydroxylation were the main metabolic pathways. We fully clarified the chemical constituents of PXC and provided a scientific and efficient strategy for rapid discovery and identification of prototypes and their metabolites in rat plasma using high-resolution MS aided by Global Natural Product Social and Compound Discoverer software.     

Rapid characterization of the chemical constituents of Cortex Fraxini by homogenate extraction followed by UHPLC coupled with Fourier transform ion cyclotron resonance mass spectrometry and GC–MS

Cortex Fraxini is an important traditional Chinese medicine. In this work, a rapid and reliable homogenate extraction method was applied for the fast extraction for Cortex Fraxini, and the method was optimized by response surface methodology. Ultra high performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry and gas chromatography with mass spectrometry were established for the separation and characterization of the constituents of Cortex Fraxini. Liquid chromatography separation was conducted on a C₁₈ column (150 mm × 2.1 mm, 1.8 μm), and gas chromatography separation was performed on a capillary with a 5% phenyl‐methylpolysiloxane stationary phase (30 m × 0.25 mm × 0.25 mm) by injection of silylated samples. According to the results, 33 chemical compounds were characterized by liquid chromatography with mass spectrometry, and 11 chemical compounds were characterized by gas chromatography with mass spectrometry, and coumarins were the major components characterized by both gas chromatography with mass spectrometry and liquid chromatography with mass spectrometry. The proposed homogenate extraction was an efficient and rapid method, and coumarins, phenylethanoid glycosides, iridoid glycosides, phenylpropanoids, and lignans were the main constituents of Cortex Fraxini. This work laid the foundation for further study of Cortex Fraxini and will be helpful for the rapid extraction and characterization of ingredients in other traditional Chinese medicines.     

Analysis of the constituents in rat plasma after oral administration of Shexiang Baoxin pill by HPLC‐ESI‐MS/MS

A valid method using liquid chromatography coupled with electrospray ionization (ESI) and ion trap mass spectrometry was established for the study of the absorbed components in rat plasma after oral administration of a traditional Chinese medicine (TCM) Shexiang Baoxin pill. The plasma was deproteinated by adding methanol prior to liquid chromatography, in which separation was carried out on a Symmetry C₁₈ column (5 µm, 250 × 4.6 mm). A linear gradient with 0.5% formic acid–water–acetonitrile was used as mobile phase. Mass spectra were acquired in both negative and positive modes. Twenty‐one components including 17 components from Shexiang Baoxin pill and four metabolites were observed from a comprehensive analysis of the chromatography of Shexiang Baoxin pill, controlled plasma and dosed plasma. All of the 17 prototype compounds and three of the metabolites were identified by comparing their retention behaviors and MS and MS/MS spectra with reference compounds and literature data. This study developed an integrated method for screening the bioactive constituents in plasma after oral adminstration of Chinese herbal medicine and provided helpful chemical information for further pharmacology and active mechanism research on TCM. Copyright © 2009 John Wiley & Sons, Ltd.     

Comparative analysis of volatile constituents between recipe jingfangsan and its single herbs by GC‐MS combined with alternative moving window factor analysis method

Comparative analysis of volatile constituents between recipe jingfangsan and its single herbs was performed by GC‐MS combined with alternative moving window factor analysis (AMWFA), a new chemometric resolution method. Identification of the compounds was also assisted by comparison of temperature‐programmed retention indices (PTRIs) on the OV‐1 column with authentic samples. In total, 36, 29, and 42 volatile components in essential oil of Herba schizonepetae (HS), Radix saposhnikoviae (RS), and the recipe were respectively determined qualitatively and quantitatively, accounting for 81.80, 82.62 and 85.98% total contents of volatile oil of HS, RS, and the recipe respectively. Analysis by the method of AMWFA indicates that there are 22 common volatile constituents between the recipe and single herbal medicine HS, and 14 common volatile constituents between the recipe and single herb medicine RS. The experimental results also show that the volatile components of the recipe in number are almost addition of that of two single herbal medicines HS and RS, and are mainly from the single herbal medicine HS.     

Pharmacokinetics study of multiple components absorbed in rat plasma after oral administration of Stemonae radix using ultra‐performance liquid‐chromatography/mass spectrometry with automated MetaboLynx software analysis

Stemonae radix (Stemona tuberosa Lour, Bai Bu) is a traditional Chinese medicinal (TCM) plant known for its antitussive and anti‐ectoparasitic activity; however, the in vivo pharmacokinetic of its multiple bioactive components remains unknown. In this article, UPLC‐Q‐TOF‐high‐definition mass spectrometry (HDMS) coupled with automated data analysis MetaboLynx? software together were first developed to screen the potentially bioactive components in the rat plasma after oral administration of Stemonae radix. Time course of the absorbed components of Stemonae radix was built to evaluate pharmacokinetic behaviors. This rapid automated analysis method was successfully applied for identification, screening, and monitoring of the 28 constituents absorbed and metabolized studies of Stemonae radix after oral administration to rats. The results showed that the ongoing changes of 28 constituents including eight parent compounds and 20 metabolites in vivo were observed to find biomarkers. From the angle of behavior in vivo, it suggested that croomine and tuberostemonine would be potential efficacy markers. This work also demonstrated that the pharmacokinetics‐based UPLC‐Q‐TOF‐HDMS can provide a reliable means of identifying and screening potentially bioactive components contributing to pharmacological effects of medicinal herbs, and to better clarify its action mechanism, further prospecting natural products in the search for new leads in drug discovery.     

Identification of metabolites in WZS‐miniature pig urine after oral administration of Danshen decoction by HPLC coupled with diode array detection with electrospray ionization tandem ion trap and time‐of‐flight mass spectrometry

Danshen (DS) is a widely used traditional Chinese medicine for treating cardiovascular and cerebrovascular diseases. A simple, rapid and sensitive method was developed for identification of the in vivo metabolites in urine of WZS‐miniature pigs after oral administration of DS decoction by HPLC coupled with diode array detection with electrospray ionization tandem ion trap and time‐of‐flight mass spectrometry. This method has been successfully applied to simultaneous identification of 50 compounds (including 11 new ones) in pig urine. In addition, one new compound, (3‐hydroxyphenyl) crylic acid glycine methyl ester (C1), along with eight known ones were first isolated by column chromatography and identified by spectroscopic means, including 1D/2DNMR and mass spectrometry, as reference substances. Ten phenolic compounds (protocatechuic aldehyde, protocatechuic acid, caffeic acid, danshensu, ferulic acid, isoferulic acid, rosmarinic acid and salvianolic acid A/B/D) were found to be the main absorbed original constituents of DS decoction, which underwent the metabolic reactions of glucuronidation, sulfation, methylation, hydrogenation and glycine conjugation in vivo. In conclusion, the developed method is applicable to the analysis and identification of constituents in biological matrices after administration of DS decoction. Copyright © 2012 John Wiley & Sons, Ltd.     

Plasma pharmacochemistry combined with microdialysis to screen potential bioactive components and their metabolites in Anemarrhena asphodeloides saponin extract using ultrahigh‐performance liquid chromatography/quadrupole‐time‐of‐flight mass spectrometry

Although various techniques have been employed to analyze drug metabolites, the metabolism of multicomponent herbal medicine has seldom been fully addressed. In contrast to chemical drugs, a number of compounds in herbal medicine could get into circulation and then be metabolized. Metabolism study on active constituents in herbal medicine is a good way for us to explain and predict a variety of events related to the efficacy and toxicity of herbal medicine. The present work aims to elucidate the multicomponent metabolic characteristics of a herbal medicine by the combination of plasma pharmacochemistry and microdialysis sampling. Anemarrhena asphodeloides, a well‐known traditional Chinese medicine, was chosen as a model. After oral administration of A. asphodeloides saponin extract to rats, microdialysis samples were collected continuously in the jugular vein and analyzed by ultrahigh‐performance LC/quadrupole‐TOF MS. The identification of compounds in biosamples was achieved by accurate mass measurement and detailed fragmentation pathway analysis. The results showed that unbound constituents in blood circulation of the rat included seven parent saponins and six metabolites, which might be the potential active components in vivo. Among which, three metabolites have not been previously reported and were identified in this study. It is the first report on systemic metabolism of total saponins of A. asphodeloides in mammalian plasma.     

Rapid characterization of the absorbed chemical constituents of Tangzhiqing formula following oral administration using UHPLC–Q‐TOF‐MS

Tangzhiqing formula, a Chinese herbal formula, is used for the treatment of type II diabetes and prediabetes. Although its effectiveness has been certified by clinical use, its absorbed chemical constituents are not comprehensively represented. Thence, in order to reveal potential bioactive components and metabolism of Tangzhiqing formula, an ultra‐high performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry method was developed. A total of 86 absorbed components, including 38 prototype compounds and 48 metabolites, were identified in rat plasma, urine, and feces after oral administration of Tangzhiqing formula. This was the first systematic study on the chemical constituents and metabolic profiling of Tangzhiqing formula. The results indicated that alkaloids and flavonoids were main absorbed components, and glucuronidation and sulfation were the major metabolites. Moreover we concluded that alkaloids and flavonoids first underwent demethylation and hydrolysis reactions before biotransformed to phase II metabolites. This study provided valuable data for safety estimation of Tangzhiqing formula, which will be advantageous for clinical application.     

Characterization of multiple absorbed constituents in rats after oral administration of Paederia scandens decoction

Paederia scandens (Lour.) Merri. (Jishiteng in Chinese) is a Chinese traditional medicine widely used in treating various diseases. However, its active components have remained unknown. In the present study, a rapid and sensitive method by high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-MSn) techniques was employed to investigate the absorbed constituents in rats after oral administration of Paederia scandens decoction. By comparing their MS data with those of authentic compounds and published data, a total of six compounds (paederosid, 1; paederosidic acid, 2; paederosidic acid methyl ester, 3; 6-hydroxy geniposide, 4; asperuloside, 5; and deacetyl asperuloside, 6) were identified in the P. scandens decoction samples. In addition, a total of seven compounds, including three iridoid glucosides and four of their metabolites, were identified in rat urine samples after administration. In addition, six compounds, including four iridoid glucosides and two of their metabolites, were identified in rat serum samples after administration. Our results significantly narrow the range of potentially active compounds in P. scandens decoction, and build a solid foundation for future research on its mechanism.     

Analysis of phenolic and triterpenoid compounds in licorice and rat plasma by high‐performance liquid chromatography diode‐array detection,time‐of‐flight mass spectrometry and quadrupole ion trap mass spectrometry

High‐performance liquid chromatography with diode‐array detection (HPLC/DAD), time‐of‐flight mass spectrometry (HPLC/TOFMS) and quadrupole ion trap mass spectrometry (HPLC/QITMS) were used for separation and identification of several compounds in licorice and rat plasma after oral administration of the herbal extract. Three phenolic compounds and one triterpenoid in licorice extract were unambiguously identified by comparing with the standard compounds. A formula database of known compounds in licorice was established, against which the other 42 compounds were identified effectively based on the accurate extract masses and formulae acquired by HPLC/TOFMS. In order to differentiate the isomers, tandem mass spectrometry was also used. The deduced fragmentation behaviors in QITMS were used to distinguish seven groups of isomers in licorice. By means of the three detectors, 46 compounds in licorice were identified. After oral administration of the extract, 25 compounds in rat plasma were detected and identified by comparing and contrasting the compounds measured in licorice with those in the plasma samples by HPLC/TOFMS. It is concluded that a rapid and effective method based on three analytical techniques was established, which is useful for identification of multiple compounds in licorice in vitro and in vivo. The result should be very useful for the quality control and curative mechanism study of licorice. Copyright © 2009 John Wiley & Sons, Ltd.     

Characterization of chemical components of Periplocae Cortex and their metabolites in rats using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry

Periplocae Cortex, named Xiang-Jia-Pi in China, has been widely used to treat autoimmune diseases, especially rheumatoid arthritis. However, the in vivo substances of Periplocae Cortex remain unknown yet. In this study, an ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used for profiling the chemical components and related metabolites of Periplocae Cortex. A total of 98 constituents were identified or tentatively characterized in Periplocae Cortex: 42 C21 steroidal glycosides, 10 cardiac glycosides, 23 organic acids, 4 aldehydes, 7 triterpenes, and 12 other types. Among them, 18 components were unambiguously identified by comparison with reference standards. In addition, 176 related xenobiotics (34 prototypes and 142 metabolites) were screened out and characterized in rats’ biosamples (plasma, urine, bile, and feces) after the oral administration of Periplocae Cortex. Moreover, the metabolic fate of periplocoside S-4a, a C21 steroidal glycoside, was proposed for the first time. In summary, phase II reactions (methylation, glucuronidation, and sulfation), phase I reactions (hydrolysis reactions, oxygenation, and reduction), and their combinations were the predominant metabolic reactions of Periplocae Cortex in rat. It is the first report to reveal the in vivo substances and metabolism feature of Periplocae Cortex. This study also provided meaningful information for further pharmacodynamics study of Periplocae Cortex, as well as its quality control research.