Study on degradation kinetics of epalrestat in aqueous solutions and characterization of its major degradation products under stress degradation conditions by UHPLC-PDA-MS/MS / 药物分析学报

Drug stability is closely related to drug safety and needs to be considered in the process of drug production, package and storage. To investigate the stability of epalrestat, a carboxylic acid derivative, a reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed in this study and applied to analyzing the degradation kinetics of epalrestat in aqueous solutions in various conditions, such as dif-ferent pH, temperatures, ionic strengths, oxidation and irradiation. The calibration curve was A=1.6 × 105C–1.3 × 103 (r=0.999) with the liner range of 0.5–24 μg/mL, the intra-day and inter-day precision was less than 2.0%, as was the repeatibility. The average accuracy for different concentrations was more than 98.5%, indicating that perfect recoveries were achieved. Degradation kinetic parameters such as degradation rate constants (k), activation energy (Ea) and shelf life (t0.9) under different conditions were calculated and discussed. The results indicated that the degradation behavior of epalrestat was pH-dependent and the stability of epalrestat decreased with the rised irradiation and ionic strength;however, it was more stable in neutral and alkaline conditions as well as lower temperatures. The results showed that the degradation kinetics of epalrestat followed first-order reaction kinetics. Furthermore, the degradation products of epalrestat under stress conditions were identified by UHPLC-PDA-MS/MS, with seven degradation products being detected and four of them being tentatively identified.

Metabonomic study on the anti-liver injury effect of Si-Ni-San on rats by using UPLC-MS/MS / 药学学报

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.

Study on Content Change of Ester Alkaloids in Aconite Processing and Compatibility with Chinese Rhubarb / 世界科学技术-中医药现代化

This study was aimed to establish an HPLC method to simultaneous determine 6 kinds of monoester and diester aconitum alkaloids. The content of alkaloids in aconite roots, black and white prepared lateral root of aconite and the compatibility of aconite roots with rhubarb were determined. This study provided reference for the interpreta-tion of the attenuation of processing and compatibility of medicines from chemical component aspect. The HPLC analysis was performed on a Phenomenex Gemini C18 (4.6 mm í 250 mm, 5 μm) with 40 mmol·L-1 ammonium ac-etate (adjusted to pH 9.8 with ammonia water) and acetonitrile as mobile phase, with a gradient elution at the flow rate of 1.0 mL·min-1 and a detection wavelength of 235 nm. The results showed that 6 alkaloids in aconite roots achieved favorable separation and a good linearity relationship (r > 0.999) over the studied concentration range. The extraction recoveries were ranged from 96.9% to 102.4% for the 6 alkaloids. The content of diester alkaloids de-creased markedly in processed products and the compatibility of aconite roots with rhubarb compared with the raw a-conite roots. It was concluded that this method was stable, reliable, simple and practical. It can be used for the si-multaneous determination of 6 kinds of monoester and diester aconitum alkaloids in aconite roots. This processing and compatibility can significantly reduce the content of alkaloids in aconite roots in order to reduce its toxicity.

Metabonomic study on protective effect of ethanol extracts of drynariae rhizoma on osteoporosis in rats urine by using UPLC-MS/MS / 中国中药杂志

This paper was designed to study metabonomic characters of the osteoporosis induced by high dose of hydrocortisone and the protective effects of Drynariae Rhizoma, which can replenish the kidney and strengthen the bones. A urinary metabonomics method based on ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS) was developed. Clear separation of healthy control group, model group and treatment group was achieved by using the principal components analysis (PCA) and 9 significantly changed metabolites were identified as potential biomarkers of osteoporosis. Compared with the health control group, the model group rats showed lower levels of creatinine, citric acid, azelaic acid, hippurate, tryptophan and indoxyl sulfate together with higher levels of phenylalanine, cresol sulfate and phenaceturic acid. These changes in urinary metabolites suggest that the disorders of amino acid metabolism, energy metabolism, gut microflora and anti-oxidative damage are related to osteoporosis induced by high dose of hydrocortisone and the potential effect of Drynariae Rhizoma on all the four metabolic pathways.

Study on in vitro and in vivo material base of Sini San by UPLC-PDA-MS/MS / 中国中药杂志

<p><b>OBJECTIVE</b>To analyze chemical constituents of Sini San its migrating components in rat plasma and study its in vitro and in vivo material base using ultra-performance liquid chromatography coupled with photo-diode-array detector and tandem mass spetrometry (UPLC-PDA-MS/MS).</p><p><b>METHOD</b>ACQUITY UPLC BEH C18 column (2.1 mm x 100 mm, 1.7 microm) was adopted, with gradient elution system of water containing 2 mmol x L(-1) ammonium acetate and acetonitrile at flow rate of 0.2 mL x min(-1). The column temperature was maintained at 35 degrees C. The mass spectra were obtained by electrospray ionization source operating in both positive and negative ion mode. Ions were scanned from the m/z 100 to 1 000, and the characteristic ions were schizolysised twice to obtain the secondary MS data.</p><p><b>RESULT</b>Twenty chemical constituents were detected, including paeoniflorin, glycyrrhizic acid, saikosaponins a and naringin. In vivo, there were 8 ingredients directly absorbed into blood after the administration of Sini San decoction, such as paeoniflorin, naringin and hesperidin. Besides, 6 metabolites were also detected, involving glucuronides, sulfate and sulfoglucuronides.</p><p><b>CONCLUSION</b>In vitro and in vivo chemical materials of Sini San decoction is analyzed by UPLC-PDA-MS/MS to reflect in vitro and in vivo material base of Sini San decoction in a comprehensive and rapid manner and provide basis for further study on efficacious material basis of Sini San decoction.</p>

LC-MS/MS method for quantification and pharmacokinetic study of gabapentin in human plasma / 药学学报

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.

Simultaneous assay of epimedin A epimedin B, epimedin C and icariin in herba epimedii by QAMS / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a new method and validate its feasibilities for quality evaluation of Fructus Epimedii.</p><p><b>METHOD</b>Four main effective flavones, epimedin A, epimedin B, epimedin C and icariin were selected as analytes to evaluate the quality of Fructus Epimedii. The relative correction factors (RCF) of icariin to the other three flavones were calculated. The method was evaluated by comparison of the quantitative results between external standard method and QAMS method.</p><p><b>RESULT</b>No significant differences were found in the quantitative results of three flavones by external standard method and QAMS method.</p><p><b>CONCLUSION</b>It is feasible and accurate to evaluate the quality of Fructus Epimedii.</p>

Isolation and identification of chemical constituents of fruits of Acanthopanax sessiliflorus / 中国中药杂志

<p><b>OBJECTIVE</b>To isolate and elucidate the chemical constituents of the fruits of Acanthopanax sessiliflorus.</p><p><b>METHOD</b>Isolation and purification were carried out on the column chromatography of silica gel and Sephadex LH-20. Their structures were elucidated on basis of physicochemical properties and spectral data.</p><p><b>RESULT</b>Nine compounds were isolated and identified as oleanolic acid-3-O-6'-O-methyl-beta-D-glucuronopyranoside (1), 22-alpha-hydroxychiisanogenin (2), oleanolic acid-3-O-beta-D-glucuronopyranoside (3), oleanolic acid-3-O-beta-D-glucopyranoside (4), oleanolic acid (5), chiisanogenin (6), (-)-sesamin (7), daucosterol (8), beta-sitosterol (9).</p><p><b>CONCLUSION</b>Compound 1 is obtained from the genus Acanthopanax genus for the first time. Compounds 2-5 are isolated from this plant for the first time.</p>

Quality Standard of Desheng Pills / 中国药房

OBJECTIVE:To establish the quality standard of Desheng pills. METHODS:The components Leonurus japonicus,Bupleurum chinense and Aucklandia lappa in Desheng pills were qualitatively identified by TLC,and the content of peoniflorin in Desheng pills was determined by HPLC. RESULTS:The TLC spots of L. japonicus,B. chinense and A. lappa were clear. The linear range of peoniflorin was 1.40～28.0 ?g?mL-1(r=0.999 0) with an average recovery of 99.4%(RSD=1.5%,n=9). CONCLUSION:The established standard can be used for the quality control of Desheng pills.