AIM: The metabolites of scutellarin were studied in gastrointestinal tract.METHODS: Scutellarin was hydrolyzed with hydrochloric acid and ?-glucuronidase.Human intestinal flora and scutellarin were incubated in vitro.The metabolites were identified by UPLC-MS/MS method.RESULTS: Scutellarin could be hydrolyzed with hydrochloric acid and ?-glucuronidase,and could be metabolized by human intestinal bacteria.A main metabolite,scutellarein,also was found in the plasma of healthy volunteers after oral administration.CONCLUSION: There were scutellarin and scutellarein in intestinal before absorption.It was suitable for scutellarin pharmacokinetic studies to determine scutellarein or total aglycone.

0.05), meanwhile,after being treated with higher-dose Huangkui Capsule,there were no significant differences for theophylline pharmacokinetics in rats,but AUC_(0-24 h) of chlorzoxazone after treatment was 1.75 times larger than that before treatment(P

AIM: To illuminate the therapeutic basis of Compound Wurenchun Capsules in combination with serum pharmacology,the lignans of this preparation migrating to blood of rats after oral administration having been accomplished. METHODS: By UPLC-MS/MS method, lignans migrating to blood were affirmed by comparing the extracted ion chromatography (EIC) of the serum containing drug with the ones of Compound Wurenchun Capsules, the control serum and control articles, correlated ion peak in mass-spectrogram were analyzed at the same time. RESULTS: Five lignans migrating to blood have been found, they are schisandrin, schisandrol B, schisantherin, deoxyschizandrin and schisandrin B. CONCLUSION: Five lignans above mentioned are likely the effective substances of Compound Wurenchun Capsules in human body. More study by means of combining with serum pharmacology will illuminate the therapeutic basis of this preparation.

Objective To identify the drug-induced constituents in rat serum containing drug of Compound Wurenchun Capsula and determine the content of these constituents. Methods Identification of the drug-induced constituents in serum has been carried out by combinative method of HPLC-DAD and UPLC-MS/MS. The content of four lignans in serum has been detected by HPLC-UV. Results Seven of eight original form compounds in serum have been identified as schisandrin,gomisin J,schisandrol B,deoxyschizandrin,gomisin N,schisandrin B,and schisandrin C. The UV spectrogram of five metabolites showed the absorption character of dibenzocyclooctadiene lignans. Eight lignans were identified by UPLC-MS/MS,besides schisantherin,there are seven lignan-like ones detected by HPLC-DAD. The content of schisandrin,schisandrol B,deoxyschizandrin,and schisandrin B in serum was (8.145 3?1.020 2),(6.604 5?1.341 4),(0.560 1?0.137 5),and (5.933 0?0.966 6) ?g/mL,respectively. ConclusionLignans and their metabolites are composed of the main drug-induced constituents in rat serum.

AIM:To research the absorption mechanism of aesculin across Caco-2 monolayer model.METHODS:The Caco-2 cell monolayers drug transport model was assigned to study the double transport mechanism of aesculin to explore the absorption of aesculin according as time and drug concentration determined through HPLC and the P_ app was calcalated.RESULTS:In the Caco-2 monolayer model,the transport of aesculin form Apical to Basolateral was similar to the transport form basolateral to apical.CONCLUSION:The main mechanism of the aesculin intestinal absorption in the Caco-2 monolayer model is passive transference.

0.05).Conclusion When given concomitantly as a Cocktail,theophylline,chlorzoxazone and dapsone have no pharmacokinetic interaction,which could be used together to evaluate CYP1A2,CYP2E1 and CYP3A4 activity.

Aim To establish a LC-MS/MS method for the determination of pirfenidone(BT)and its major metabolite 5-carboxy-pirfenidone(SBT)in human plasma.Methods Human plasma samples containing BT and SBT,as well as their corresponding deuterium-labeled internal standards pirfenidone-d5(dBT)and 5-carboxy-pirfenidone-d5(dSBT),were precipitated using methanol.Chromatographic separation was carried out on an Agilent ZORBAX SB C18(3.0 mm×100 mm,3.5 μm)column with the mobile phase of water(0.5％formic acid)and acetonitrile(50/50).The detection of analytes was performed on a tandem mass system equipped with an electrospray ionization source in positive ion mode using multiple-reaction monitoring.The MS/MS ion transitions monitored were m/z 185.958→77.1 for BT,m/z 215.944→77.0 for SBT,m/z 190.965→81.1 for dBT and m/z 220.948→99.1 for dSBT.Results There was no remarkable interference in blank solvent,plasma,and there was no mutual interference between analytes or internal standards.The proposed method showed good linearity over the concentration range of 0.020 59～25.14 mg·L-1 for BT and 0.016 73～20.42 mg·L-1 for SBT.The intra-batch and inter-batch precision and accuracy were proved to be acceptable.Human samples kept stable after 4 h at room temperature,the three freeze-thaw cycles and 10,29 and 52 days at-70 ℃,and the processed samples remained stable after 24 h in the autosampler.The average extraction recovery and matrix effect were precise,reproducible and acceptable.Conclusion Our current LC-MS/MS method is proved to be sensitive,accurate and convenient,and could be suitable for the clinical pharmacokinetic studies of BT-related preparations.

Clinically, kidney?yang deficiency is one of the main TCM syndromes in patients with major depressive disorder. Warming yang and reinforcing kidney as a therapeutic measure for the treatment of depressive disorder has a?chieved good clinical curative effect. However, there are some problems on the study of kidney?yang deficiency depression. One of the reasons is that the establishment methods of depression animal model with kidney?yang deficiency are not uni?fied. In order to provide reference and further improve the replication method of depression animal models with kidney?yang deficiency, we systematically collected and analyzed the experiment results published in the past 15 years about the depres?sion animal model with kidney?yang deficiency induced by glucocorticoid hormone drugs and find out their similarities and differences.

Aim To establish an UPLC-ESI-MS method for determination of asiaticoside and investigate its application to pharmacokinetic study in rats.Methods Eight rats were given 40 mg·kg~(-1) asiaticoside iv respectively.Drug plasma concentration was determined by UPLC-ESI-MS.Pharmacokinetic parameters were evaluated.Results Calibration curves were linear over 0.038～7.6 mg·L~(-1) and LLOQ was 38 μg·L~(-1),the recoveries of asiaticoside from plasma were larger than 95%,and RSD of inter-day and intra-day assay were below 10%.After iv administration of 40 mg·kg~(-1) asiaticoside,the pharmacokinetic parameters of AUC(0-t),T(1)/(2)β,CL,Vd were (81 443.67±57 156.81) μg·L~(-1)·min~(-1),(23.44±9.60) min,(0.19±0.07) L·min~(-1)·kg~(-1),(8.92±6.68) L·kg~(-1),respectively.Conclusion The method described in this report was sensitive and specific,and suitable for pharmacokinetic studies of asiaticoside in rats.

Aim To investigate the pharmacokinetic effect of aspirin on caffeic acid in dengzhanxixin injec-tion( DI) . Methods Concentration of caffeic acid in rat plasma was detected by LC-MS/MS after rats were given intravenous administration of DI or DI combined with aspirin by gavage. Pharmacokinetic parameters were calculated by DAS 1. 0 pharmacokinetic software. Results In vivo pharmacokinetic models of caffeic acid were two-compartment open models in both the caffeic acid group and the caffeic acid combined with aspirin group. After compatibility, caffeic acid showed a significant increase in T 12β, with a slight decrease in CL. Conclusions Aspirin can reduce metabolic process of caffeic acid in vivo.