The effect of tripterygium glucoside tablet on pharmacokinetics of losartan and its metabolite EXP3174 in rats

Losartan and tripterygium glucoside tablet (TGT) are often simultaneously used for reducing urine protein excretion in clinic. However, it is unknown whether there is potential herb–drug interaction between losartan and TGT. The aim of this study was to investigate their potential herb–drug interaction, and clarify the mechanism of the effect of TGT on the pharmacokinetics of losartan and its metabolite EXP3174 in rats. The plasma concentrations of losartan and EXP3174 were determined by LC–MS, and the main pharmacokinetic parameters were calculated. The C _max, t _1/2 and AUC_{(0–t )} of losartan became larger after co‐administration, while the C _max and AUC_{(0–t )} of EXP3174 became smaller, suggesting that TGT could influence the pharmacokinetics of losartan and EXP3174. The effects of TGT and its main components on the metabolic rate of losartan were further investigated in rat liver microsomes. Results indicated that TGT and its two main ingredients could decrease the metabolic rate of losartan. Therefore, it was speculated that TGT might increase the plasma concentration of losartan and decrease the concentration of EXP3174 by inhibiting the metabolism of losartan. The results could provide references for clinical medication guidance of losartan and TGT to avoid the occurrence of adverse reactions.     

Rapid determination of losartan and losartan acid in human plasma by multiplexed LC–MS/MS

A rapid LC–MS/MS method has been developed and validated for the determination of losartan (LOS) and its metabolite losartan acid (LA) (EXP‐3174) in human plasma using multiplexing technique (two HPLC units connected to one MS/MS). LOS and LA were extracted from human plasma by SPE technique using Oasis HLB® cartridge without evaporation and reconstitution steps. Hydroflumethiazide (HFTZ) was used as an internal standard (IS). The analytes were separated on Zorbax SB C‐18 column. The mass transition [M–H] ions used for detection were m/z 421.0 → 127.0 for LOS, m/z 435.0 → 157.0 for LA, and m/z 330.0 → 239.0 for HFTZ. The proposed method was validated over the concentration range of 2.5–2000 ng/mL for LOS and 5.0–3000 ng/mL for LA with correlation coefficient ?0.9993. The overall recoveries for LOS, LA, and IS were 96.53, 99.86, and 94.16%, respectively. Total MS run time was 2.0 min/sample. The validated method has been successfully used to analyze human plasma samples for applications in 100 mg fasted and fed pharmacokinetic studies.     

Drug–drug interactions between moxifloxacin and rifampicin based on pharmacokinetics in vivo in rats

Moxifloxacin and rifampicin are all the first‐line options for the treatment of active tuberculosis, which are often combined for the treatment of multidrug resistance pulmonary tuberculosis in clinic. However, the potential drug–drug interactions between moxifloxacin and rifampicin were unknown. The aim of this study was to investigate the drug–drug interactions between moxifloxacin and rifampicin based on their pharmacokinetics in vivo after oral administration of the single drug and both drugs, and reveal their mutual effects on their pharmacokinetics. Eighteen male Sprague–Dawley rats were randomly assigned to three groups: moxifloxacin group, rifampicin group and moxifloxacin + rifampicin group. Plasma concentrations of moxifloxacin and rifampicin were determined using LC‐MS at the designated time points after drug administration, and the main pharmacokinetic parameters were calculated. In addition, effects of moxifloxacin and rifampicin on their metabolic rate and absorption were investigated using rat liver microsome incubation systems and Caco‐2 cell transwell model. The main pharmacokinetic parameters of moxifloxacin including T_max, C_max, t_1/2 and AUC_(0–t) increased more in the moxifloxacin + rifampicin group than in the moxifloxacin group, but the difference was not significant (p > 0.05). However, the pharmacokinetic parameters of rifampicin, including peak concentration, area under the concentration–time curve, half‐life and the area under the first moment plasma concentration–time curve, increased significantly (p < 0.05) compared with the rifampicin group, and the time to peak concentration decreased significantly (p < 0.05). The mean residence time of rifampicin also increased in moxifloxacin + rifampicin group compared with the rifampicin group, but the difference was not significant (p > 0.05). The rat liver microsome incubation experiment indicated that moxifloxacin could increase the metabolic rate of rifampicin from 23.7 to 38.7 min. However, the Caco‐2 cell transwell experiment showed that moxifloxacin could not affect the absorption rate of rifampicin. These changes could enhance the drug efficacy, but they could also cause drug accumulation, which might induce adverse effect, so it was suggested that the drug dosage should be adjusted and the drug concentration in plasma should be monitored if moxifloxacin and rifampicin are co‐administered. Copyright © 2016 John Wiley & Sons, Ltd.     

The comparative pharmacokinetics of four bioactive ingredients after administration of Ramulus Cinnamomi–Radix Glycyrrhizae herb pair extract,Ramulus Cinnamomi extract and Radix Glycyrrhizae extract

Ramulus Cinnamomi (RC)–Radix Glycyrrhizae (RG) is a classic herb pair, which is commonly used as a fixed form to treat cardiovascular disease in the clinic. Our work aimed to compare the pharmacokinetic difference of cinnamic acid, liquiritin, isoliquiritigenin and glycyrrhetinic acid in rats after oral administration of the RC–RG herb pair extracts [Guizhigancao Decoction (GGD) and Lingguizhugan Decoction (LGZGD)] and the single RC or RG extract. A HPLC‐MS method was developed and validated to study comparative pharmacokinetics. The pharmacokinetic parameters (C_max, AUC, MRT) of four compounds between the RC–RG herb pair group and the single herb (RC or RG) group showed significant differences (p < 0.05). Compared with the single herb (RC or RG) group, higher peak concentration, slower elimination and larger exposure could be observed after giving the RC–RG herb‐pair extracts. The pharmacokinetic differences might indicate the relativity of remedy in the RC–RG herb pair and provide scientific information for rational administration of the drug in the clinic. Copyright © 2016 John Wiley & Sons, Ltd.     

Comparative pharmacokinetic study of two boswellic acids in normal and arthritic rat plasma after oral administration of Boswellia serrata extract or Huo Luo Xiao Ling Dan by LC‐MS

Huo Luo Xiao Ling Dan (HLXLD), a Chinese herbal formula composed of 11 different herbs, has been used traditionally for the treatment of arthritis and other chronic inflammatory diseases. However, the pharmacokinetic profile of its anti‐inflammatory bioactive compounds has not been elucidated. Boswellic acids are the bioactive compounds with potent anti‐inflammatory activity isolated from Boswellia serrate which is one of the 11 herbs of HLXLD. The objective of the study was to compare the pharmacokinetics of the two bioactive bowsellic acids: 11‐keto‐β‐boswellic acid and 3‐O‐acetyl‐11‐keto‐β‐boswellic following oral administration of HLXLD or Boswellia serrata extract alone in normal and arthritic rats. An LC‐MS method was developed and validated for the determination of 11‐keto‐β‐boswellic acid and 3‐O‐acetyl‐11‐keto‐β‐boswellic in the comparative pharmacokinetic study. The results showed that there were significant differences in pharmacokinetic parameters between normal and arthritic groups. Interestingly, the absorptions of two boswellic acids were significantly higher in HLXLD than Boswellia serrata extract alone, indicating the synergistic effect of other herbal ingredients in HLXLD. This comparative pharmacokinetic study provided direct evidence supporting the notion that the efficacy of a complex mixture such as HLXLD is better than that of single components in treating human diseases. Copyright © 2014 John Wiley & Sons, Ltd.     

Simultaneous determination of losartan and active metabolite EXP3174 in rat plasma by HPLC with column switching

Summary A new liquid chromatographic method with columnswitching has been developed for the simultaneous determination of losartan and its active metabolite, EXP3174 in rat plasma. The plasma samaple was injected onto a precolumn of Lichroprep RP-8 after dilution with 5% acetonitrile in 50 mM phosphoric acid. Polar plasma components were eluted using this diluent. After valve switching, the concentrated drugs were eluted in the back-flush mode and separated by an Inertsil ODS-2 column with acetonitrile-acetate buffer. The method showed excellent precision, accuracy and speed with detection limit 20 ng mL^–1. Total analysis time per sample was less than 40 min and the coefficients of variation for intra and inter-assay were 4.8%. This method has been successfully applied after oral administration of losartan to rat plasma samples.     

Application of column‐switching HPLC method in evaluating pharmacokinetic parameters of zaltoprofen and its salt

The objective of this study was to compare the pharmacokinetic parameters of zaltoprofen and those of its sodium salt in rats. Zaltoprofen, a potent non‐steroidal anti‐inflammatory agent, was virtually insoluble in water, but its sodium salt had excellent water solubility. To investigate the effect of aqueous solubility differences upon their pharmacokinetic parameters, minicapsules containing the drug powders were administrated orally to rats, and blood samples were taken via the common carotid artery. A column‐switching high‐performance liquid chromatographic analytical procedure was developed and validated for the quantitation of zaltoprofen in rat plasma samples. Our study demonstrated that the time required to reach maximum plasma concentration (T_max) of zaltoprofen sodium was significantly reduced and its maximum plasma concentration (C_max) was increased 1.5‐fold, relative to the values for zaltoprofen. It is anticipated that the sodium salt of zaltoprofen will allow the rapid onset of the drug's action in the treatment of inflammatory diseases. Copyright © 2008 John Wiley & Sons, Ltd.     

Influence of Moringa oleifera on pharmacokinetic disposition of rifampicin using HPLC‐PDA method: a pre‐clinical study

The influence of active fraction isolated from pods of an indigenous plant, Moringa oleifera (MoAF) was studied on the pharmacokinetic profile of the orally administered frontline anti‐tuberculosis drug rifampicin (20 mg/kg b.w.) in Swiss albino mice. The antibiotic rifampicin alone and in combination with MoAF (0.1 mg/kg b.w.) was administered orally and heparanized blood samples were collected from the orbital plexus of mice for plasma separation at 0, 1, 2, 3, 4 and 5 h, post treatment. Plasma rifampicin concentration, pharmacokinetic parameters and drug metabolizing enzyme (cytochrome P‐450) activity were determined. The pharmacokinetic data revealed that MoAF‐treated animals had significantly increased rifampicin plasma concentration, C_max, K_el, t_½(a), t_½(el), K_a and AUC as well as inhibited rifampicin‐induced cytochrome P‐450 activity. In conclusion, the result of this study suggested that the bioavailability‐enhancing property of MoAF may help to lower the dosage level and shorten the treatment course of rifampicin. Copyright © 2010 John Wiley & Sons, Ltd.     

Simultaneous determination of eight bioactive components of Cirsium setosum flavonoids in rat plasma using triple quadrupole LC/MS and its application to a pharmacokinetic study

Cirsium setosum (Willd.) MB. has been reported to exert significant anti‐hemorrhagic, anti‐inflammation, antimicrobial, sedative and detoxicating efficacy. It has been widely used to treat gastrointestinal bleeding, uterine bleeding, infectious hepatitis and cardiovascular disease in China. Recent studies have shown that flavonoids are the main active components in C. setosum. Nevertheless, to the best of our knowledge, there is no report concerning the simultaneous determinations and pharmacokinetics of constituents in C. setosum flavonoids in rat plasma. In this study, a rapid, sensitive and selective triple quadrupole liquid chromatography–mass spectrometry method was developed to determine eight analytes from the flavonoids of C. setosum in rat plasma. In addition, the pharmacokinetic study of the eight analytes in rats after oral administration of C. setosum flavonoids was successfully completed through this method. According to the pharmacokinetic parameters of the eight analytes, rutin, naringin, quercetin, acacetin, wogonin were the long‐acting components of the C. setosum flavonoids, with long elimination time and high bioavailability. Of note, the method developed in this study fills a blank in pharmacokinetic studies of C. setosum flavonoids. Our findings provide valuable views on the understanding of the absorption mechanism of C. setosum flavonoids and their clinical efficacy.     

Simultaneous determination of losartan,EXP-3174 and hydrochlorothiazide in plasma via fully automated 96-well-format-based solid-phase extraction and liquid chromatography–negative electrospray tandem mass spectrometry

An automated, sensitive and high-throughput liquid chromatographic/electrospray tandem mass spectrometric (LC–MS/MS) assay was developed for the simultaneous determination of losartan (LOS), its major circulating metabolite EXP-3174 and hydrochlorothiazide (HCTZ) in human plasma. LOS and HCTZ coexist in the same drug formulation, and this is the first method that enables the simultaneous determination of both drugs along with the active metabolite of LOS. Since these drugs have different physicochemical properties, the employment of a liquid–liquid extraction (LLE) protocol was precluded. A fully automated solid-phase extraction (SPE) protocol, based on 96-well format plates, was used to isolate these compounds and furosemide (internal standard, IS) from plasma. Washing and elution steps were amended accordingly in order to minimize any matrix effect from components of the plasma without reducing the elution of the molecules of interest. The compounds were eluted from a C18 column and detected with an API 3000 triple-quadrupole mass spectrometer using negative electrospray ionization and multiple reaction monitoring (MRM). The assay was linear over the range 1.00–400 ng/mL for LOS and EXP-3174 and 0.500–200 ng/mL for HCTZ, respectively, when 200 μl of plasma was used in the extraction. The overall intra- and interassay variations were within acceptance limits. The analysis time for each sample was 4 min, and more than 300 samples could be analyzed in one day by running the system overnight. The assay was simple, highly sensitive, selective, precise, fast, and it enables the reliable determination of LOS, EXP-3174 and HCTZ in pharmacokinetic or bioequivalence studies after per os administration of a single tablet containing both drugs.     

A convenient synthesis by microwave irradiation of an active metabolite (EXP-3174) of losartan

A novel and convenient microwave-assisted synthesis of an active metabolite (EXP-3174) of losartan is described. Room temperature and microwave irradiation of the reactions are compared. Synthesis by microwave irradiation gave the desired compound in higher yields and in shorter reaction times than those obtained at room temperature.     

去甲万古霉素群体药代动力学与药效学优化研究

目的研究去甲万古霉素群体药代动力学指标差异,对患者进行药效学优化。方法选取2015年1月至2015年12月268例感染患者,将其按照年龄分为中青年组和老年组,每组各134例,采用群体药代动力学和药效学优化公式进行计算,分析患者上述指标差异。结果青年组与老年组的群体药代动力学各项指标差异明显具有统计学意义(P0.05)。结论感染患者通过去甲万古霉素药物治疗疗效确切,对革兰阳性菌的杀灭作用明显,采用群体药代动力学和药效学研究后发现,AUC24/MIC能够作为去甲万古霉素的应用指标,并以此指导临床用药效果显著,值得临床应用推广。     

A new approach for pharmacokinetic studies of natural products: measurement of isoliquiritigenin levels in mice plasma,urine and feces using modified automated dosing/blood sampling system

The present study was undertaken to investigate the pharmacokinetics of isoliquiritigenin (isoLQ) as determined by the automated dosing/blood sampling (ABS) and traditional manual blood sampling techniques in awake and freely moving mice using combined liquid chromatography tandem mass spectrometry. Pharmacokinetic comparison was conducted by allocating mice into two groups; an ABS group (intravenous study and oral studies, n = 5 each) and a manual group (intravenous and oral studies; n = 5 each). Significant differences in pharmacokinetic parameters (area under the curve and clearances) were observed between ABS and manual groups. This could be mainly due to the blood sampling site difference (via heart puncture in traditional manual group and via carotid artery in ABS groups). The low F of isoLQ could be mainly due to a considerable gastrointestinal and/or hepatic first‐pass effect and not to incomplete absorption. The driving force for distribution and elimination of drugs is its concentration in the arterial blood. Therefore, the ABS method was found to be a useful drug development tool for accelerating the process of preclinical in vivo studies and for obtaining reliable and accurate pharmacokinetic parameters in mice. Copyright © 2013 John Wiley & Sons, Ltd.     

Pharmacokinetic comparisons by UPLC‐MS/MS of isomer paeoniflorin and albiflorin after oral administration decoctions of single‐herb Radix Paeoniae Alba and Zengmian Yiliu prescription to rats

Zengmian Yiliu (ZMYL), a traditional Chinese formula, is designed to improve clinical efficacy and reduce adverse effects in combination with cisplatin in ovarian cancer chemotherapy. In ZMYL, Radix Paeoniae Alba (RPA, made from root of Paeonia lactiflora Pall.) acts as an adjunctive drug in cancer treatment by ameliorating side effects induced by radio‐ and chemotherapy. The pharmacokinetics differences between isomer albiflorin and paeoniflorin, the main components of RPA, after oral administration decoction of single‐herb RPA and ZMYL were compared using a sensitive and accurate UPLC‐MS/MS. The results indicate that there are statistically significant differences between the pharmacokinetic parameters: decreasing area under the plasma concentration–time curve (AUC), maximum concentration (C_max), elimination rate constant (K_e) and increasing apparent volume of distribution (V_d) and clearance (CL) for albiflorin, increasing distribution half‐life (T_1/2d) and decreasing elimination half‐life (T_1/2e), distribution rate constant (K_d) and absorption rate constant (K_a) for paeoniflorin in the ZMYL group compared with the single‐herb RPA group. In comparison with albiflorin, the pharmacokinetic parameters of paeoniflorin included significantly increasing mean residence time (MRT) and V_d, decreasing CL and K_e in the single‐herb RPA group and increasing MRT and T_1/2d and decreasing CL, K_e and K_d in the ZMYL group. Both paeoniflorin and albiflorin are more likely, as the main active ingredients in RPA and ZMYL, to play a variety of pharmacological effects, and herb–herb interactions occur, resulting in different pharmacokinetics of albiflorin and paeoniflorin in RPA and ZMYL. Copyright © 2014 John Wiley & Sons, Ltd.     

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.     

Bioanalytical methods for the determination of itraconazole and hydroxyitraconazole: overview from clinical pharmacology,pharmacokinetic, pharmacodynamic and metabolism perspectives

Itraconazole represents an important therapeutic option for the treatment of fungal infections. Itraconazole undergoes rapid metabolism to form hydroxyitraconazole, which also contributes to the anti‐fungal activity exhibited by the parent compound. Since both itraconazole and hydroxyitraconazole are effective inhibitors of cytochrome P450 (CYP) 3A4 and p‐glycoprotein (pgp)‐mediated efflux transporters, they have the potential to elicit drug–drug interaction with a number of CYP3A4 and/or pgp substrates. This review focuses on providing comprehensive details on the bioanalytical methods available for the quantitation of both itraconazole and hydroxyitraconazole. Additionally, it provides an overview of the clinical pharmacology (several case studies of drug–drug interactions), pharmacokinetics, pharmacodynamics and metabolism related aspects of itraconazole. Copyright © 2009 John Wiley & Sons, Ltd.     

Anti‐inflammatory activities and glycerophospholipids metabolism in KLA‐stimulated RAW 264.7 macrophage cells by diarylheptanoids from the rhizomes of Alpinia officinarum

Alpinia officinarum is used for its anti‐inflammatory activity historically in China. Diarylheptanoids isolated from A. officinarum play important biological roles in the prevention and treatment of inflammatory disorders. Seven diarylheptanoids (1–7) were isolated from A. officinarum. The cell viabilities and anti‐inflammatory activities of diarylheptanoids were evaluated by MTT assay and tumor necrosis factor‐α production in Kdo2‐lipid A‐stimulated RAW 264.7 cells in vitro. The relationships between their anti‐inflammatories and structure‐activities are discussed. The results indicated that compounds 1 and 3–7 had significant anti‐inflammatory activities. The relationships between inflammation and phospholipids metabolism were elucidated by multivariate data analysis. Twenty‐two potential biomarkers were identified in inflammatory group vs. blank group, and 11 potential biomarkers were identified for inflammatory group vs. drug‐treatment groups. Ten common phospholipids were characterized. On the basis of a previous study in our laboratory, we found that phosphatidylethanolamine (18:0/18:1) might be the important glycerophospholipid biomarker in inflammation. In this study, we firstly combined anti‐inflammatory activities and glycerophospholipids changes of traditional Chinese medicine. This work suggests that the anti‐inflammatory activities of diarylheptanoids might be significantly related to glycerophospholipids and could provide a useful database for investigating the anti‐inflammatory effects of traditional Chinese medicine.     

A sensitive liquid chromatography–mass spectrometry bioanalytical assay for a novel anticancer candidate – ZMC1

ZMC1 {azetidinecarbothioic acid, [1‐(2‐pyridinyl) ethylidene] hydrazide} is a lead compound being developed as one of the first mutant p53 targeted anti‐cancer drugs. Establishing a precise quantitative method is an integral component of this development. The aim of this study was to develop a sensitive LC/MS/MS assay suitable for assessing purity, stability and preclinical pharmacokinetic studies of ZMC1. Acetonitrile protein precipitation extraction was chosen for plasma sample preparation with satisfactory recovery (84.2–92.8%) for ZMC1. Chromatographic separation was achieved on an Xterra C₁₈ column (50 × 4.6 mm, 3.5 µm) using a gradient elution with mobile phase of 0.1% formic acid in water and acetonitrile. ZMC1 and internal standard 2‐amino‐6‐bromobenzothiazole were identified using selected‐ion monitoring mode at m/z 235.2/178.2 and m/z 231.0/150.0 at retention times of 5.2 and 6.3 min, respectively. The method was validated with a linearity range of 3.9–500.0 ng/mL in human plasma and showed acceptable reproducibility with intra‐ and interday precisions <5.9 and 10.5%, and accuracy within ±5.4% of nominal values. This analytical method together with basic stability data in plasma and plasma binding experiments provides a reliable protocol for the study of ZMC1 pharmacokinetics. This will greatly facilitate the pre‐clinical development of this novel anti‐cancer drug. Copyright © 2015 John Wiley & Sons, Ltd.     

Simultaneous determination of kaempferol,quercetin, mangiferin,gallic acid,p‐hydroxybenzoic acid and chlorpheniramine maleate in rat plasma after oral administration of Mang‐Guo‐Zhi‐Ke tablets by UHPLC‐MS/MS and its application to pharmacokinetics

Mang‐Guo‐Zhi‐Ke tablets (MGZKTs) is an effective Chinese patent medicine. It contains mango leaf extract as the main raw material and the antihistamine drug, chlorpheniramine maleate is included in the formulation. However, its pharmacokinetic effect is rarely reported. A highly sensitive, reliable and rapid high‐throughput method using ultra‐high‐performance liquid chromatography with tandem mass spectrometry (UHPLC‐MS/MS) was used to simultaneously determine kaempferol, quercetin, mangiferin, p‐hydroxybenzoic acid, gallic acid and chlorpheniramine maleate in rat plasma after oral administration of MGZKTs. The method was successfully developed and fully validated to investigate the pharmacokinetics of MGZKTs. Chloramphenicol and clarithromycin were used as internal standards (IS). A practicable protein precipitation procedure with methanol was adopted for sample preparation. The samples were separated on an Acquity UHPLC Syncronis C₁₈ column (100 × 2.1 mm, 1.7 μm) using 0.1% formic acid–acetonitrile as the mobile phase. The flow rate was set at 0.4 mL/min. The obtained calibration curves were linear in the concentration range of ~1–1000 ng/mL for plasma (r > 0.99). Method validation results met the criteria reported in the US Food and Drug Administration guidelines. Quercetin, p‐hydroxybenzoic acid and kaempferol were absorbed rapidly and reached the peak concentration between 0.16 and 0.25 h. This validated that the UHPLC‐MS/MS method was successfully applied to study the pharmacokinetic parameters of the six compounds in rat plasma after oral administration of MGZKTs. This evidence will be useful for the clinical rational use of Mang‐Guo‐Zhi‐Ke tablets.     

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.