ABSTRACT
Objective:To improve the quality standard of Shenwei Gubi tablets， and to explore the reasons for the great difference in the contents of quality control index components between batches of this product. Method:The fingerprint of this product was established by HPLC， the determination was performed on Diamonsil C18 column （4.6 mm×250 mm， 5 μm） with acetonitrile （A）-0.1% phosphoric acid solution （B） for gradient elution （0-5 min， 10%A； 5-15 min， 10%-12%A； 15-30 min， 12%-26%A； 30-43 min， 26%-31%A， 43-50 min， 31%-40%A， 50-70 min， 40%-55%A； 70-84 min， 55%-72.5%A） as the mobile phase at detection wavelength of 230 nm. The orthogonal partial least squares-discriminant analysis-variable importance in the projection （OPLS-DA-VIP） map was drawn with the common peak as the independent variable. The contribution of 26 common peaks to the fingerprint differences among different batches of this product was quantified. By searching for the chromatographic peaks with great differences， combined with relevant literature， the components related to the clinical indications of the product were screened out and their contents were determined by specificity experiment， and the quantitative indicators were finally selected. HPLC-doide array detector （DAD） was employed to determine the contents of the above preferred indexes with detection wavelengths of 236， 276， 230， 322 nm， other conditions were the same as HPLC fingerprint detection method. Result:A total of 26 common peaks were calibrated on the HPLC fingerprint of Shenwei Gubi tablets. The similarity between the fingerprint of each batch samples and the reference fingerprint was≥0.950. Loganic acid， gentiopicroside， paeoniflorin and osthole were optimized as the quantitative indicators of this product， their average contents were 161.02， 401.80， 255.54， 80.68 μg·g-1. Conclusion:The established fingerprint and multi-index quantitative analysis method are stable and reliable， and can be used for quality control of Shenwei Gubi tablets. Difference in contents of quality control components between batches of raw materials and the imperfect quality control method of intermediates in the production process are the main reasons for the great difference in the contents of quality control indicators between batches of this product.
ABSTRACT
Venetoclax is a selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2（BCL-2）and has great potential in treating a variety of hematological tumors. In recent years, domestic and foreign scholars have tried to use venetoclax singal or in combination with some drugs to treat the patients with hematological tumors, including elderly acute myeloid leukemia（AML）patients un suitable for intensive chemotherapy, relapsed or refractory chronic lymphocytic leukemia（CLL）, Non-Hodgkin's lymphoma（NHL）and multiple myeloma（MM）patients, these studies have achieved good results．At the same time，some scholars found that the secondary drug-resistance occurred in some patients who continuous treated with Venetoclax, and explored the Venetoclax-resistant mechanism. In this review, the research advance of Venetoclax in hematological tumors and the mechanisms of drug resistance are summarized and discussed briefly.
Subject(s)
Aged , Humans , Antineoplastic Agents , Therapeutic Uses , Bridged Bicyclo Compounds, Heterocyclic , Therapeutic Uses , Hematologic Neoplasms , Leukemia, Lymphocytic, Chronic, B-Cell , Drug Therapy , SulfonamidesABSTRACT
<p><b>OBJECTIVE</b>To develop and validate a sensitive method for quantitative analysis of podophyllotoxin in blood and dermal microdialysis samples of rats based on liquid chromatography-tandem mass spectrometry (UFLC-MS-MS).</p><p><b>METHODS</b>The microdialysis samples were prepared by liquid-liquid extraction using ethyl acetate with etoposide as the internal standard (IS). Podophyllotoxin was separated with an Agilent ZORBAX XDB-C18 column (2.1 mmx50 mm, 3.5 microm). The mobile phase consisted of acetonitrile: 10 mmol/L ammonium acetate (40:60, V/V) at a flow rate of 0.3 ml/min and the analysis was performed at the ambient temperature. The UFLC-MS/MS system was operated in the mode of multiple reaction monitoring using the electrospray ionization technique in positive mode.</p><p><b>RESULTS</b>Podophyllotoxin and etoposide responses were optimized at the transitions m/z 432.7-->397.3 and 589.5-->229.5, respectively. Calibration curves were linear over the range 2.0-1000 ng/ml. The lowest limits of quantification and detection values were 2.0 ng/ml and 0.7 ng/ml, respectively. The inter- and intra-day precision and accuracy were both less than 15%.</p><p><b>CONCLUSION</b>This selective and sensitive method can be used to quantity podophyllotoxin in the blood and dermal microdialysates of rats.</p>
Subject(s)
Animals , Rats , Chromatography, Liquid , Methods , Microdialysis , Methods , Podophyllotoxin , Blood , Pharmacokinetics , Sensitivity and Specificity , Skin , Metabolism , Tandem Mass Spectrometry , MethodsABSTRACT
Objective To investigate the effects of enteral nutrition with galactooligosaccharides (GOS) on serum inflammatory cytokines in rats with severe acute pancreatitis (SAP). Methods SD rats were randomly divided into sham operation control group, SAP with enteral nutrition (EN) group and SAP with EN supplemented with GOS (GOS-EN) group, and each group was divided into 4 d and 7 d subgroups according to the time that animals were sacrificed (n=8 in each subgroup). Rat SAP models were established by injection of 38 g/L sodium taurocholate beneath the pancreatic capsule. The serum amylase, inflammatory cytokines TNF-α, IL-2 and IL-10 were detected. Results At each time point, the levels of serum amylase in all SAP groups were significantly higher than those in sham operation control group (P < 0.01), and the levels in GOS-EN group were significantly lower than those in EN group (P < 0.01). The levels of serum TNF-α and IL-10 in all SAP groups were significantly higher than those in sham operation control group (P < 0.01), while the levels of IL-2 in all SAP groups were significantly lower than those in sham operation control group. The levels of TNF-α in GOS-EN group were significantly lower than those in EN group (P <0.05), while the levels of IL-2 and IL-10 and the ratio of IL-10/TNF-α were significantly higher than those in GOS-EN group (P < 0.05). Conclusion Early EN supplemented with GOS could modulate the balance of pro- and anti-inflammatory response.
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To develop a sensitive and specific high performance liquid chromatography-tandem mass spectrometric (HPLC-MS/MS) method for the determination of mosapride in human plasma, mosapride and internal standard tamsulosin were extracted from plasma with liquid-liquid extraction, then separated on a Waters ACQUITY UPLC BEH C18 column (50 mm x 2.1 mm, 1.7 microm ID) with gradient elution at flow-rate of 0.25 mL x min(-1). The mobile phase was water (containing 0.3% formic acid) and acetonitrile under gradient conditions. Electrospray ionization (ESI) source was applied and operated in the positive ion mode. Multiple reaction monitoring (MRM) mode with the transitions of m/z 422 --> m/z 198 and m/z 409 --> m/z 228 were used to quantify mosapride and the internal standard, respectively. The linear calibration curve was obtained in the concentration range of 0.17 - 68.00 ng x mL(-1). The lower limit of quantification was 0.17 ng x mL(-1). The inter- and intra-day precision (RSD) was less than 13%, and the accuracy (RE) was within +/- 6.3% calculated from QC samples. The method was used to determine the concentration of mosapride in plasma after a single oral dose of 5 mg mosapride citrate to 20 healthy male Chinese volunteers. The method has been proved to be selective, sensitive, rapid and suitable for pharmacokinetic study of mosapride.
Subject(s)
Humans , Male , Administration, Oral , Area Under Curve , Benzamides , Blood , Pharmacokinetics , Chromatography, High Pressure Liquid , Methods , Gastrointestinal Agents , Blood , Pharmacokinetics , Morpholines , Blood , Pharmacokinetics , Sensitivity and Specificity , Serotonin Receptor Agonists , Blood , Pharmacokinetics , Spectrometry, Mass, Electrospray Ionization , Tandem Mass Spectrometry , MethodsABSTRACT
Objective To investigate the effect of intra-articular carboxymethylated ehitosan(CM- CTS)injection on inducible nitric oxide synthase(iNOS)expression in cartilage at the early stage of os- teoarthfitis(OA).Methods Thirty-two white rabbits were underwent unilateral anterior cruciate ligament transection(ACLT)and were randomly divided into 4 groups 5 weeks after transection.Rabbits of group A re- ceived 0.3 ml of 2% high molecular weight CMCTS(H-CMCTS)once every two weeks.Rabbits in group B were treated using 2% low molecular weight(L-CMCTS)CMCTS at:the same intervals.Group C rabbits were injected intra-articularly with 0.3 ml of 1% sodium hyaluronate(Na-HA)once a week.Animals of group D were not injected.At sacrifice,11 weeks following surgery,the expression of iNOS in cartilages was analyzed by immunohistochemistry and reverse transcription-polymerase chain reaction(RT-PCR)methods.Results Both immunohistochemistry and RT-PCR showed that the level of iNOS expression of cartilage in CMCTS in- jection groups was lower than that in Na-HA injection group and the untreated group.There was no significant difference in iNOS expression between the two different molecular weight CMCTS injection groups. No signifi- cant difference of iNOS expression in cartilage was found between Na-HA injection group and the untreated group.Conclusion CMCTS suppresses iNOS expression in cartilage during the early stage of OA.Na-HA treatment has no effect on iNOS expression in cartilage.