ABSTRACT
A UPLC-MS/MS method based on metabonomic skills was developed to study the serum metabolic changes of rats after acute liver injury induced by CCl4 and to evaluate the action mechanism of Si-Ni-San. The integrated data were exported for principal components analysis (PCA) by using SIMCA-P software, in order to find the potential biomarkers. It showed that clear separation of healthy control group, model group, silymarin group, Si-Ni-San group was achieved by using the PCA method. Nine significantly changed metabolites were identified as potential biomarkers of acute liver injury. Compared with the health control group, the model group rats showed higher levels of phenylalanine, tryptophan and GCDCA together with lower levels of LPC 16 : 0, LPC 18 : 0, LPC 18 : 1, LPC 16 : 1, LPC 20 : 4 and LPC 22 : 6. These changes of serum metabolites suggested that the disorders of amino acid metabolism, lipid metabolism, bile acid biosynthesis and anti-oxidative damage were related to acute liver injury induced by CCl4. Si-Ni-San might have the anti-liver injury effect on all these four metabolic pathways.
Subject(s)
Animals , Male , Rats , Carbon Tetrachloride Poisoning , Chemical and Drug Induced Liver Injury , Blood , Chromatography, High Pressure Liquid , Methods , Drugs, Chinese Herbal , Pharmacology , Glycodeoxycholic Acid , Blood , Lysophosphatidylcholines , Blood , Metabolomics , Phenylalanine , Blood , Plants, Medicinal , Chemistry , Principal Component Analysis , Random Allocation , Rats, Sprague-Dawley , Tandem Mass Spectrometry , Tryptophan , BloodABSTRACT
<p><b>OBJECTIVE</b>To study the effect of phenformin hydrochloride that may be illegally added in traditional Chinese medicine preparations on the pharmacokinetics of puerarin in rats.</p><p><b>METHOD</b>Rats were randomly divided into the single pueraria group and the phenformin hydrochloride combined with pueraria group. After oral administration in the two groups, their bloods were sampled at different time points to determine the drug concentration of puerarin in rat blood and calculate pharmacokinetic parameters.</p><p><b>RESULT</b>After oral administration with pueraria extracts and phenformin hydrochloride combined with pueraria extracts, the two groups showed main pharmacokinetic parameters as follows: Cmax were (2.39 +/- 1.01), (1.03 +/- 0.35) mg x L(-1), respectively; Tmax were (0.50 +/- 0.09), (1.5 +/- 0.5) h, respectively; Ke were (0.153 +/- 0.028), (0.172 +/- 0.042) h(-1), respectively; t(1/2) were (4.65 +/- 0.86), (4.20 +/- 0.81) h, respectively; AUC(0-t), were (5.73 +/- 2.60), (5.45 +/- 1.81) mg x h x L(-1), respectively; AUC(0-infinity) were (6.72 +/- 2.89), (6.26 +/- 1.88) mg x h x L(-1), respectively. Compared with the single puerarin group, the Cmax was significantly decreased (P < 0.05) and the Tmax was markedly longer (P < 0.01) than the hydrochloride combined with pueraria group.</p><p><b>CONCLUSION</b>Phenformin hydrochloride can slow down the absorption process of puerarin and change the pharmacokinetic process of puerarin to some extent.</p>
Subject(s)
Animals , Male , Rats , Administration, Oral , Drug Interactions , Hypoglycemic Agents , Pharmacology , Isoflavones , Pharmacokinetics , Phenformin , Pharmacology , Rats, Wistar , Vasodilator Agents , PharmacokineticsABSTRACT
A sensitive, rapid and specific liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for quantification of gabapentin in human plasma has been developed. After a single plasma protein precipitation with methanol, gabapentin and metformin (internal standard) were chromatographed on a Inertsil ODS-3 column (50 mm x 2.1 mm ID, 3 microm) with mobile phase consisting of methanol-0.2% formic acid aqueous solution (80:20, v/v) at a flow-rate of 0.2 mL x min(-1). Electrospray ionization (ESI) source was applied and operated in the positive ion mode. Multiple reaction monitoring (MRM) mode with the transitions of m/z 172 --> m/z 154 and m/z 130 --> m/z 71 were used to quantify gabapentin and metformin, respectively. The run time was 2.2 min. The linear calibration curve was obtained in the concentration range of 40.8-8.16x10(3) ng x mL(-1). The lower limit of quantification was 40.8 ng x mL(-1). The intra- and inter-day precision (RSD) was less than 12%, and the accuracy (RE) was within +/-6.4% calculated from quality control (QC) samples. The method was used to determine the concentration of gabapentin in human plasma after a single oral administration of 600 mg gabapentin capsule to 20 healthy male Chinese volunteers. The method was proved to be selective, sensitive, rapid and suitable for pharmacokinetic study of gabapentin in human plasma.
Subject(s)
Humans , Male , Administration, Oral , Amines , Blood , Pharmacokinetics , Anticonvulsants , Blood , Pharmacokinetics , Area Under Curve , Chromatography, High Pressure Liquid , Cyclohexanecarboxylic Acids , Blood , Pharmacokinetics , Spectrometry, Mass, Electrospray Ionization , Tandem Mass Spectrometry , gamma-Aminobutyric Acid , Blood , PharmacokineticsABSTRACT
<p><b>OBJECTIVE</b>To determine two flavonoid compounds in Psoralea corylifolia L. (PC) simultaneously with HPLC method.</p><p><b>METHOD</b>Bavachin and corylin isolated from PC and purified in our laboratory were used as the reference compounds. The HPLC separation was carried out on an Techsphere ODS column using mobile phase consisting of a mixture of methanol and 20 mmol.L-1 ammonium acetate buffer pH 4.0 (67:33), and the UV detection wavelength was 240 nm.</p><p><b>RESULT</b>Simultaneous determination of bavachin and corylin was achieved. The linear range was 1.25-20 micrograms.mL-1 for both bavachin and corylin. The average recovery of bavachin and corylin was 94.9% and 96.2%, and RSD was 3.1% and 3.6% respectively.</p><p><b>CONCLUSION</b>This is the first report on simultaneous determination of bavachin and corylin in PC with satisfactory accuracy and reproducibility.</p>