Identification of the absorbed constituents and metabolites of Huangqi Guizhi Wuwu decoction by ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Huangqi Guizhi Wuwu decoction (HGWWD) is a widely used traditional Chinese medicine (TCM) preparation for the treatment of ischemic stroke and diabetes peripheral neuropathy. However, the material basis for the efficacy of HGWWD remains unclear. In this study, a rapid, sensitive and selective ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method was developed to separate and identify the absorbed components and metabolites of HGWWD in rat plasma after oral administration for the first time. By comparing the retention time, high-resolution mass spectrometry primary and secondary mass spectrometry data of blank plasma and drug-containing plasma, a total of 42 constituents, including 24 prototype compounds and 18 metabolites, were identified or tentatively characterized. The results indicated that monoterpenes, flavonoids, organic acids, amino acids, gingerols and alkaloids were main prototype compounds in rat plasma, and flavonoid-related metabolites, organic acid-related metabolites and gingerol-related metabolites were major metabolites. It is concluded the developed UHPLC-Q-TOF-MS method with high sensitivity and resolution is suitable for identifying and characterizing the absorbed components and metabolites of HGWWD, and the results will provide important data for further study on the relationship between the chemical constituents and pharmacological activities of HGWWD.

Characterization of chemical constituents in Huangqi Guizhi Wuwu decoction using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Huangqi Guizhi Wuwu decoction (HGWWD) is a classic traditional Chinese medicine prescription for the treatment of ischemic stroke, etc. However, the material basis of its efficacy remains unclear, seriously affecting drug development and clinical applications. In the present study, an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry method was developed to separate and identify the chemical components of HGWWD. A total of 81 compounds were identified and tentatively characterized. Eight compounds were accurately identified by comparing the retention time and mass spectrometry data with those of reference substances, the remaining compounds were characterized by comparing the mass spectrometry data and reference information. Based on the results of compound attribution, 35 compounds were from Astragali Radix, six compounds were from Cinnamomi Ramulus, 23 compounds were from Paeoniae Radix Alba, eight compounds were from Zingiberis Rhizoma Recens and nine compounds were from Jujubae Fructus. The results showed that monoterpenoids, flavonoids, organic acids, triterpenes, amino acids, gingerols, alkaloids, and glycosides were the main chemical components of HGWWD. This analytical method is suitable for characterizing the chemical constituents of HGWWD, and the results provide important information for elucidating its pharmacodynamic material basis and mechanism of action.

Comparison of IDA, SWATH, and MSALL techniques in the analysis of compounds of Huangqi Guizhi Wuwu decoction by UHPLC-Q-TOF-MS.

Huangqi Guizhi Wuwu decoction (HGWD) is an effective traditional Chinese medicine prescription, which is used for treating blood arthralgia in the clinic. However, its material basis has not been studied yet. Herein, a new and highly sensitive ultra-high-performance liquid chromatography-quadrupole-time of flight-MS (UHPLC-Q-TOF-MS) technique is proposed and used for the high-resolution and accurate identification of the material basis of HGWD. Seventy-eight compounds have been identified in HGWD. The advantages of information-dependent acquisition (IDA), sequential window acquisition of all theoretical fragment-ion spectra (SWATH), and MSALL in the quantitative and qualitative analyses of compounds were compared. For the identification of compounds, the best mode with the highest accuracy is the IDA. For the quantification of compounds, MSALL shows the best repeatability and linearity. This research provides a theoretical basis for the study of quality control of traditional Chinese medicine preparations.

Effects of terbuthylazine on myocardial oxidative stress and ferroptosis via Nrf2/HO-1 signaling pathway in broilers.

Terbuthylazine (TBA) is one of the most commonly used and effective herbicides. However, due to its affinity for soil organic matter and water solubility, TBA can lead to biological health concerns. This study exposed broilers to TBA (0 mg/kg bw, 0.4 mg/kg bw, 4 mg/kg bw) for 28 days. The results showed significant pathological damage in broiler myocardial tissue, such as widening of the interstitial space, rupture of muscle fibers, and deposition of myocardial collagen fibers. In addition, Under the 0.4 mg/kg bw TBA exposure, myocardial oxidative stress was observed in broilers, which was accompanied by the activation of Nrf2/HO-1 pathway and the increased protein and mRNA levels of NQO1, NOX2 and SOD2 antioxidant enzymes. However, Nrf2/HO-1 protein and mRNA levels were reversed at 4 mg/kg bw TBA exposure. Meanwhile, the Nrf2/HO-1 mediated antioxidant defense was impaired. In contrast with the low dose, the protein and gene expression levels of NQO1, NOX2, and SOD2 were reduced in 4 mg/kg bw TBA group. The expression of GPX4 and SLC7A11 was significantly downregulated at both protein and mRNA levels. Beyond that, ACSL4 expression was significantly up-regulated, and the protein result was consistent with the mRNA expression, demonstrating the occurrence of ferroptosis. In general, TBA exposure activated the Nrf2/HO-1 pathway, resulting in ferroptosis. This study links ferroptosis to the Nrf2/HO-1 pathway, providing new insights into the potential role of TBA in myocardial toxicity.

Chemical Profiling, Quantitation, and Bioactivities of Ginseng Residue.

Ginseng residue is a by-product stemming from the commercial extraction of ginsenosides. To assess the disparities between ginseng residue and ginseng tablet, we employed the ultra-high-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) technique for sample analysis. The analyses revealed the presence of 39 compounds in both ginseng residue and ginseng tablets. Subsequently, the contents of total ginsenosides and total ginseng polysaccharides in the ginseng residue and ginseng tablet were determined. The results indicate that while only a small fraction of ginsenosides remained in the ginseng residue, a significant amount of polysaccharides was retained. Furthermore, our evaluation encompassed the antioxidant activities of both ginseng residue and ginseng tablets. Notably, ginseng residue exhibited robust antioxidant effects, thereby showcasing its potential for recycling as a functional food raw material.

Chemical Differentiation and Quantitative Analysis of Black Ginseng Based on an LC-MS Combined with Multivariate Statistical Analysis Approach.

Black ginseng is a new type of processed ginseng that is traditionally used in herbal medicine in East Asian countries. It is prepared from fresh, white, or red ginseng by undergoing a process of steaming and drying several times. However, the chemical differentiation of black ginseng with different processing levels is not well understood. The aim of this study was to propose a new method for discriminating and quantifying black ginseng. Six ginsenosides from black ginseng were accurately quantified, and based on this, the black ginseng samples were divided into incomplete and complete black ginseng. Ultrahigh-performance liquid chromatography-quadrupole-time of flight/mass spectrometry (UPLC-Q-TOF/MS) combined with a multivariate statistical analysis strategy was then employed to differentiate the two groups. A total of 141 ions were selected as analytical markers of black ginseng, with 45 of these markers being annotated by matching precise m/z and MS/MS data from prior studies.

A pseudotargeted method based on sequential window acquisition of all theoretical spectra mass spectrometry acquisition and its application in quality assessment of traditional Chinese medicine preparation-Yuanhu Zhitong tablet.

Quality control plays a key role in the application of Chinese materia medica, especially in the preparation of traditional Chinese medicine. A pseudotargeted analysis method using an ultra-high-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry that was operated in the sequential window acquisition of all theoretical spectra mode was proposed to explore the chemical markers of traditional Chinese medicine preparation. Full-scan-based untargeted analysis was applied to extract the target ions. After data preprocessing, 302 target ions were extracted and used for the subsequent sequential window acquisition of all theoretical spectra analyses. The established sequential window acquisition of all theoretical spectra-based pseudotargeted approaches exhibited good repeatability and a wide linear range. The established method was successfully applied to discover analytical markers for the Yuanhu Zhitong tablet. After multivariate statistical analysis, 94 potential markers were identified. Ten markers were annotated by matching accurate m/z and product ion information obtained from previous reports. It is clearly indicated that the pseudotargeted analysis could make a great contribution to the quality assessment of traditional Chinese medicine preparation as a newly emerging technique.

A MSALL quantitative method for the determination of Poloxamer 188 in rat plasma by UHPLC-Q-TOF/MS and its application to pharmacokinetic study.

Poloxamer (PL)188 is a commonly used pharmaceutical excipient with unique physicochemical properties. In this study, an MSALL quantitative method for the determination of PL188 in rat plasma by UHPLC-Q-TOF/MS was developed and validated. PL188 was analyzed on PLRP-S reversed-phase column (50 × 4.6 mm, 8 µm, 1,000 Å) with mobile phase 0.1% formic acid-water and 0.1% formic acid in acetonitrile-isopropanol (2:3, v/v). The liner range was 0.1-10.0 µg/ml. A pharmacokinetic study was performed on rats at a dose of 5 mg/kg by intravenous injection. The pharmacokinetic parameters of intravenous injection were as follows: half-life was 2.0 ± 1.1 h, volume of distribution was 5.1 ± 3.2 L/kg, area under the concentration-time curve was 3.0 ± 0.6 µg/L h and clearance was 1.7 ± 0.3 L/h/kg. The results indicated that PL188 could be rapidly distributed to tissues with a high clearance rate. This study can provide a good reference for the further study of PL188.

Ultra-high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry method for quantifying polymer poloxamer 124 and its application to pharmacokinetic study.

Poloxamer is a commonly used pharmaceutical excipient. It is a high molecular polymer formed using polypropylene oxide and polyethylene oxide units. Specifically, poloxamer 124 is one of the smaller molecular weight in the poloxamer series; however, its pharmacokinetic behaviors in vivo are still unclear. In this study, a method for quantifying poloxamer 124 in rat plasma through ultra-high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry was developed. The intravenous dosage of PL124 was 10 mg/kg. Plasma was collected at different times. The calibration curve was linear in the range of 0.1-5 µg/mL for the poloxamer 124 (r ≥ 0.9956) with the lower limit of quantitation of 0.1 µg/ml. The relative standard deviation of the intraday and interday precisions was below 8.0%, and the relative error of the accuracy was within ±12.0%. The extraction recovery, matrix effect, and stability were satisfactory in rat plasma. The validated method was successfully applied to a pharmacokinetic study of poloxamer 124 in rats. Results indicated that poloxamer 124 could be rapidly absorbed and eliminated through caudal vein injection. This study is helpful for the further study of poloxamer 124.

Understanding the hepatoxicity of inorganic mercury through guts: Perturbance to gut microbiota, alteration of gut-liver axis related metabolites and damage to gut integrity.

Mercury (Hg) brings adverse effects to the environment and human beings and inorganic mercury (IHg) is a typical hepatic toxin. This work studied the impacts of IHg on gut microbes and metabolome together with its damage to liver and gut in rats through gut microbiome, metabolomics and metallomics. Sprague Dawley (SD) rats were orally exposed to 0.4 µg/mL IHg and sacrificed after 24 h. It was found that IHg perturbed greatly on the gut microbiota, such as increased pathogenic bacteria like G. bacillus. In addition, IHg also changed gut-liver axis related metabolites, which was confirmed by the secretion of a large number of inflammatory factors in both the gut and the liver. The changed gut-liver axis related metabolites correlated well to the changes of gut microbiome. In all, besides the direct deposition in liver of Hg, the perturbance to gut microbiome and alteration of gut-liver axis related metabolites by IHg also contributed to its hepatoxicity, which provides new insights about the hepatoxicity of chemicals. The strategy applied in this work may also be used to understand the hepatoxicity of other chemicals.

Tissue Distribution Study of Poloxamer188 in Rats by Ultra-High-Performance Liquid Chromatography Quadrupole Time of Flight/Mass Spectrometry with MSALL-Based Approach.

Poloxamer188 (PL188), as one of the most commonly used pharmaceutical excipients, has unique physicochemical properties and good biocompatibility, and so is playing an increasingly extensive role in the field of medicine. Currently, there are few studies on the tissue distribution of PL188 in vivo. In this study, the LC-MS method based on MSALL technique of quadrupole time of flight mass spectrometry for absolute quantitative analysis of poloxamer 188 in biological substrates was established for the first time. The tissue distribution of poloxamer188 in SD rats were studied using the established quantitative analysis method. To explore the distribution of PL188 in organs and tissues, PL188 was administered via rat tail vein at a dose of 5 mg/kg. Eight kinds of tissues including heart, liver, spleen, lung, kidney, stomach, muscle and brain of rats were collected at 0.25 h, 1 h and 4 h after administration. Tissue distributions showed the highest level was observed in kidney, then in stomach, which indicated PL188 mainly bioaccumulated in the kidney. This study can provide references for the further study of PL188.

Simultaneous determination of ferulic acid, paeoniflorin, and albiflorin in rat plasma by ultra-high performance liquid chromatography with tandem mass spectrometry: Application to a pharmacokinetic study of Danggui-Shaoyao-San.

A rapid, selective, and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry method was developed for simultaneous determination of ferulic acid, paeoniflorin, and albiflorin, the major active constituents of Danggui-Shaoyao-San, in rat plasma using geniposide as the internal standard. The plasma samples were processed by protein precipitation with acetonitrile, and then separated on a Shim-Pack XR-ODS C18 column (75 mm × 3.0 mm, 2.2 µm) using gradient elution program with a mobile phase consisting of 0.1% aqueous formic acid and acetonitrile at a flow rate of 0.4 mL/min. The detection was achieved on a 3200 QTRAP mass spectrometer equipped with electrospray ionization source in negative ionization mode. Quantification was performed using multiple reaction monitoring mode by monitoring the fragmentation of m/z 192.9→134.0 for ferulic acid, m/z 525.0→120.9 for paeoniflorin, m/z 525.2→121.0 for albiflorin, and m/z 433.1→225.1 for the internal standard, respectively. The calibration curve was linear in the range of 5-2500 ng/mL for all the three analytes (r ≥ 0.9972) with the lower limit of quantitation of 5 ng/mL. The intraday and interday precisions were below 12.1% for all the analytes in terms of relative standard deviation, and the accuracy was within ±11.5% in terms of relative error. The extraction recovery, matrix effect and stability were satisfactory in rat plasma. The validated method was successfully applied to a pharmacokinetic study of ferulic acid, paeoniflorin, and albiflorin after oral administration of Danggui-Shaoyao-San to rats.

Simultaneous determination of eight bioactive constituents of Zhi-Zi-Hou-Po decoction in rat plasma by ultra high performance liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study.

Zhi-Zi-Hou-Po Decoction, consisting of Gardenia jasminoides Ellis, Magnolia officinalis Rehd. et Wils., and Citrus aurantium L, is a classical Traditional Chinese Medicine formula for the treatment of depression. In order to make good and rational use of this formula in the future, a sensitive, selective, and reliable ultra high performance liquid chromatography with tandem mass spectrometry method was developed for simultaneous determination of two iridoid glycosides (geniposide and genipin gentiobioside), two lignans (honokiol and magnolol), four flavonoid glycosides (isonaringin, naringin, hesperidin, and neohesperidin), the major bioactive constituents of Zhi-Zi-Hou-Po Decoction, in rat plasma using paeoniflorin as internal standard. Plasma samples were pretreated by a simple protein precipitation with acetonitrile. Chromatographic separation was performed on a shim-pack XR-ODS C18 column (75 × 3.0 mm, 2.2 µm) using gradient elution with mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.5 mL/min. Mass spectrometric detection was conducted on a 3200 QTRAP mass spectrometry equipped with electrospray ionization source in negative ionization mode. Quantification was performed using multiple reactions monitoring mode. Calibration curves exhibited good linearity (r > 0.9947) over a wide concentration range for all analytes, and the lower limits of quantification were 10, 5, 1, 5, 1, 5, 1, and 5 ng/mL for geniposide, genipin gentiobioside, honokiol, magnolol, isonaringin, naringin, hesperidin, and neohesperidin, respectively. The intraday and interday precisions at three quality control levels were less than 12.3% and the accuracies ranged from -11.2 to 10.7%. Extraction recovery, matrix effect, and stability were satisfactory in rat plasma. The validated method was successfully applied to a pharmacokinetic study of the eight analytes after oral administration of Zhi-Zi-Hou-Po decoction to rats.

Simultaneous determination of ferulic acid and gastrodin of Tianshu Capsule in rat plasma by ultra-fast liquid chromatography with tandem mass spectrometry and its application to a comparative pharmacokinetic study in normal and migraine rats.

Tianshu Capsule, consisting of Ligusticum chuanxiong Hort and Gastrodia elata Blume, is a widely used Traditional Chinese Medicine preparation for the treatment of migraine. Ferulic acid and gastrodin are main active constituents in Ligusticum chuanxiong Hort and Gastrodia elata Blume, and have been used as marker components for quality control of Tianshu Capsule. In this study, a selective, sensitive, and reliable ultra-fast liquid chromatography with tandem mass spectrometry method was developed for simultaneous determination of ferulic acid and gastrodin in rat plasma using geniposide as internal standard. The plasma samples were extracted by protein precipitation with methanol after acidification and separated on a Shim-Pack XR-ODS C18 column (75 × 3.0 mm, 2.2 µm) using gradient elution with a mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.6 mL/min. Detection was performed on 3200 QTRAP mass spectrometry equipped with turbo ion spray source in negative ionization mode. Validation parameters were within acceptable ranges. The validated method was applied to compare the pharmacokinetic profiles of ferulic acid and gastrodin in normal and migraine rats. Our results showed that there were remarkable differences in the pharmacokinetic properties of the analytes between the normal and migraine groups.

Simultaneous quantitative determination of 20 active components in the traditional Chinese medicine formula Zhi-Zi-Da-Huang decoction by liquid chromatography coupled with mass spectrometry: application to study the chemical composition variations in different combinations.

Zhi-Zi-Da-Huang decoction (ZZDHD), a classical traditional Chinese medicine (TCM) prescription composed of four herbal medicines, has been widely used in treating various hepatobiliary disorders for a long time. The objective of this study was to develop a sensitive and efficient liquid chromatography coupled with mass spectrometry (LC-MS) method for quantitative determination of 20 active constituents, including three iridoid glycosides, 11 flavonoids, three anthraquinones and three tannins in ZZDHD. Separation was achieved on a phenomenex kinetex C18 column (150 × 4.6 mm, 2.6 µm) using gradient elution with a mobile phase consisting of acetonitrile and 0.1% formic acid in water. Detection was performed with electrospray ionization source in the negative ionization and selected ion monitoring mode. The established method was validated by determining the linearity (r(2) ≥ 0.9983), limit of quantification (0.16-300 ng/mL), precision (RSD ≤ 4.6%), average recovery (96.0-105.6%), repeatability (RSD ≤ 3.2%) and stability (RSD ≤ 4.5%). Then, the method was successfully applied to investigate the chemical composition variations owing to the interaction between the four component herbs of ZZDHD during the extraction process. It was found that different combinations of the herbs affect the extraction efficiency of chemical constituents in different ways. The validated LC-MS method provides a meaningful basis for quality control and further research on ZZDHD.

Deoxycholic acid-grafted PEGylated chitosan micelles for the delivery of mitomycin C.

Mitomycin C (MTC) was incorporated to a micelle system preparing from a polymer named deoxycholic acid chitosan-grafted poly(ethylene glycol) methyl ether (mPEG-CS-DA). mPEG-CS-DA was synthesized and characterized by (1)H nuclear magnetic resonance ((1)H-NMR) and Fourier transform infrared spectroscopy. mPEG-CS-DA formed a core-shell micellar structure with a critical micelle concentration of 6.57 µg/mL. The mPEG-CS-DA micelles were spherical with a hydrodynamic diameter of about 231 nm. After poly(ethylene glycol)ylation of deoxycholic acid chitosan (CS-DA), the encapsulation efficiency and drug loading efficiency increased from 50.62% to 56.42% and from 20.51% to 24.13%, respectively. The mPEG-CS-DA micelles possessed a higher drug release rate than the CS-DA micelles. For pharmacokinetics, the area under the curve (AUC) of the mPEG-CS-DA micelles was 1.5 times higher than that of MTC injection, and these micelles can enhance the bioavailability of MTC. mPEG-CS-DA micelles reduced the distribution of MTC in almost all normal tissues and had the potential to improve the kidney toxicity caused by MTC injection.

Characterization of chemical constituents in Zhi-Zi-Da-Huang decoction by ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

A sensitive and reliable ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was established to separate and identify the chemical constituents of Zhi-Zi-Da-Huang decoction, a classic traditional Chinese medicine formula. The chromatographic separation was achieved on a Shim-pack XR-ODS C18 column (75 × 3.0 mm, 2.2 µm) using a gradient elution program. The detection was performed on a Waters Xevo G2 Q-TOF mass spectrometer equipped with electrospray ionization source in both positive and negative modes. With the optimized conditions, a total of 82 compounds were identified or tentatively characterized. Of the 82 compounds, 21 compounds were identified by comparing the retention time and MS data with reference standards, the rest were characterized by analyzing MS data and retrieving the reference literature. In addition, 31 compounds were identified from Gardenia jasminoides Ellis, ten compounds were identified from Rheum palmatum L., 33 compounds were identified from Citrus aurantium L., and eight compounds were identified from Sojae Semen Praeparatum. Results indicated that iridoids, anthraquinones, flavonoids, isoflavonoids, coumarins, glycosides of crocetin, monoterpenoids, and organic acids were major constituents in Zhi-Zi-Da-Huang decoction. It is concluded that the developed ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method with high sensitivity and resolution is suitable for identifying and characterizing the chemical constituents of Zhi-Zi-Da-Huang decoction, and the analysis provides a helpful chemical basis for further research on Zhi-Zi-Da-Huang decoction.

Determination of cefuroxime lysine in rat brain microdialysates by ultra-fast liquid chromatography with UV and tandem mass spectrometry: application to an acute toxicokinetic study.

Cefuroxime lysine is a new second-generation cephalosporins, which can penetrate the blood-brain barrier to cure the meningitis. In order to investigate its acute toxicokinetic study after intraperitoneal injection of 675 mg/kg cefuroxime lysine, a sensitive and clean ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method for the determination of cefuroxime lysine in microdialysate samples was developed and validated, which was compared with UFLC-UV as a reference method. Chromatographic separation was performed on a Shim-pack XR-ODS C18 column (75 × 3.0 mm, 2.2 µm), with an isocratic elution of 0.1% formic acid in acetonitrile-0.1% formic acid in water (45:55, v/v) for LC-MS and acetonitrile-20 mm potassium dihydrogen phosphate (pH 3.0,20:80, v/v) for LC-UV. The lower limit of detection was 0.01 µg/mL for LC-MS and 0.1 µg/mL for LC-UV method, with the same corresponding linearity range of 0.1-50 µg/mL. The intra- and inter-day precisions (relative standard deviation) for both methods were from 1.1 to 8.9%, while the accuracy was all within ±10.9%. The results of both methods were finally compared using paired t-test; the results indicated that the concentrations measured by the two methods correlated significantly (p < 0.05), which suggested that the two methods based on LC-MS and LC-UV were suitable for the acute toxicokinetic study.

[Comparative study on pharmacokinetics of gentiopicroside and gentianae radix extract in rats].

OBJECTIVE: To compare the pharmacokinetics of gentiopicroside and Gentianae Radix extract in rats and assess the effect of other components in Gentianae Radix on the pharmacokinetics of gentiopicroside. METHODS: The rats were oral administrated with gentiopicroside and Gentianae Radix extract, the content of geritiopicroside was chosen as index and determined by HPLC. The pharmacokinetic parameters were calculated with DAS 2.1.1 program. RESULTS: The concentration-time curve of gentiopicroside and Gentianae Radix extract was described by two compartment model. The main pharmacokinetic parameters of gentiopicroside and Gentianae Radix extract were: C(max) (16.53 +/- 0.37) g/mL and (16.61 +/- 0.49) g/mL, T(max) 0.25 h and 1.5 h, t1/2(alpha) (0.20 +/- 0.04) h and (0.69 +/- 0. 14) h, t /2 (beta) (0.64 +/- 0.08) hand (0.80 +/- 0.11) h, AUC(0-infinity) (18.20 +/- 1.97) g x h/mL and (39.20 +/- 1.18) g x h/mL, CL( 2.75 +/- 0.32) L/(h x kg) and (1.22 +/- 0.04) L (h x kg), respectively. CONCLUSION: There are significantly differences in pharmacokinetic parameters between gentiopicroside and Gentianae Radix extract in rats.

Characterization of the Chemical Constituents in Radix gentianae by Ultra-High Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry.

Radix gentianae (RG) is a traditional Chinese medicine used for the treatment of acute and chronic hepatitis in clinic. However, the chemical profile of RG is still unconfirmed, which hindered the progress of pharmacological study and clinical application. In this study, ultra-high performance liquid chromatography together with quadrupole time-of-flight mass spectrometry techniques were employed to separate and characterize the chemical constituents in RG. Under the optimized conditions, a total of 60 compounds were rapidly identified or tentatively characterized. Results indicated that iridoid glucosides, flavonoids, organic acids, amino acids, saccharides and nucleosides were major constituents in RG. It is concluded the established method can help to clarify the substance basis and provide useful information for ascertaining the bioactive constituents and action mechanism of RG.