Current Issue : January - March Volume : 2019 Issue Number : 1 Articles : 5 Articles
A sensitive and robust liquid chromatography-tandem mass spectrometric (LC-MS/MS)\nmethod was developed and validated for the determination of nimbolide in mouse serum.\nExemestane was used as the internal standard (IS). Here, we employed acetonitrile-based protein\nprecipitation (PPT) for serum sample preparation, and performed chromatographic separation using\nan ODS Hypersil C18 column (100 mm Ã? 2.1 mm, 5...) with gradient elution (0.1% formic acid\nin water vs 100% acetonitrile). The run time was 6 min. Instrumental analysis was performed by\nelectrospray ionization tandem mass spectrometry (ESI-MS/MS) in the multiple-reaction monitoring\n(MRM) under positive mode. A good linear calibration was achieved in the 5â??1000 ng/mL range.\nThe intra- and inter-day precisions for nimbolide were ............... respectively. Intra-day\naccuracy ranged from 96.9â??109.3%, while inter-day accuracy ranged from 94.3â??110.2%. The matrix\neffect of nimbolide, detected but consistent at low and high concentrations, do not affect linearity of\nstandard curve. In conclusion, we have developed and validated a sensitive analytical method for\ndetermination of a novel natural compound nimbolide in mouse serum, and it has been successfully\napplied to our preclinical study in investigating the pharmacokinetic properties of nimbolide,\nwhich could greatly facilitate the preclinical development of the promising lead compound for\nanticancer therapy....
It is critical to assess the severity of alcohol consumption in certain diseases such as alcohol\nliver disease and alcohol addiction. Ethyl glucuronide (EtG) is a highly stable metabolite of ethanol\nin hair; thus, it was proposed as a long-term monitoring marker for alcohol consumption. Therefore,\nan HPLC-MS/MS method for EtG in hair was developed and applied to a clinical setting to assess\nthe relevance of the EtG concentration and/or the Alcohol Use Disorders Identification Test (AUDIT)\nscore to high-risk alcohol consumption. EtG was extracted from 10 mg of hair using water and\nanalyzed using on-line sample purification coupled to HPLC-MS/MS. The diagnostic performances\nof the EtG concentration and/or the AUDIT score for detecting high-risk alcohol consumption were\nstatistically evaluated between alcohol addicts (n = 44) and average alcohol users (n = 19). The on-line\nsample purification resulted in labor-saving with smaller sample amount. Both the EtG concentrations\n(4.0â??587.4 pg/mg vs. 12.9â??74.9 pg/mg) and the AUDIT scores (4â??40 vs. 5â??28) obtained from the\nalcohol addicts were significantly higher than those from the average alcohol users. The performance\nevaluation demonstrated that the integration score of the EtG concentration and the AUDIT score\nincreased diagnostic performance for high-risk alcohol consumption....
Caffeine is recognized as the first-line therapeutic agent for apnea of prematurity. The dosage regimen is 10 mg/kg loading dose\nand 2.5 mg/kg maintenance dose. However, the plasma concentration achieved, not always, is therapeutically useful. It makes\nnecessary to increase the doses to reach plasma concentration up to 30 or 35 .. or even higher to attain therapeutic effect. To\nstudy why neonates have these differences, and whether these effects are linked to prenatal caffeine exposure, we had to develop an\nanalytical method for an accurate measurement of caffeine and metabolites concentration. The analysis was carried out using fetal\nbovine serum (FBS) as biological matrix in a high-performance liquid chromatography with an ultraviolet detector method. This\nmethod allows acceptable chromatographic resolution between analytes in 15 minutes. It was validated and proved to be linear in\nthe 0.1â??40 .. range for caffeine, paraxanthine, theobromine, and theophylline in the same chromatographic analysis.\nAccuracy for quality control samples for intra- and interday assays was ranged from 96.5 to 105.2% and 97.1 to 106.2%. Precision\nhad CV no more than 10% in all concentration levels for all analytes. No differences were observed between quantification in\nhuman and FBS. This method was applied to quantify plasma drug concentration in mothers and their newborns in a Mexican\nnortheast population. In our study, we confirmed self-reported caffeine maternal intake in 85.2% (n 23); meanwhile, in their\nnewbornâ??s plasma, it was detected only in 78% (n 21). Caffeine plasma concentrations in mother and newborn had a linear\nrelationship, and no differences were observed between groups (mothers versus children). These results suggest that our analytical\nmethod and substitution of biological matrix was linear, precise, and accurate for caffeine quantification and could be used for\nmeasuring prenatal exposure and let us to study, in the future, concentration differences observed during apnea clinical treatment....
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality\nworldwide. In an attempt to understand some potential mechanisms of persistence and oncogenicity\nof Hepatitis C virus (HCV)-related HCC, microfibrillar-associated protein 4 (MFAP4), fibrotic indices\nand oxidative status biomarkers were assessed in the sera of 50 patients with HCV-associated HCC,\n25 patients with HCV-related liver cirrhosis and 15 healthy individuals. Serum oxidized Coenzyme\nQ10 (CoQ10) and malondialdehyde showed significant elevation in HCC patients compared to the\ncontrol group ..... as well as cirrhotic patients .... while serum\nglutathione content and superoxide dismutase activity were significantly decreased in HCC patients\ncompared to the control group ....... Serum MFAP4, aspartate aminotransferase to platelet\nratio index (APRI), fibrosis index based on the 4 factors (FIB-4) and Forns index showed significant\nincrease in HCC patients compared to the control group ...... while only APRI and FIB-4 were\nsignificantly different between HCC and cirrhotic patients ... with a sensitivity of 86% and\n92%, respectively, at cut off... for APRI and .... for FIB-4. Therefore, increasing oxidative stress\nand fibrosis might mediate HCV induced cirrhosis and HCC. APRI and FIB-4 may be used as a simple\nnon-expensive formula for the screening of HCC rather than MFAP4....
Stauntonia hexaphylla leaf extract (YRA-1909), which is widely used for the antirheumatic\nproperties, has been under phase 2 clinical trials in patients with rheumatoid arthritis since April 2017.\nLiquid chromatography-tandem mass spectrometric method while using liquidâ??liquid extraction\nwith ethyl acetate was validated for the simultaneous determination of the major active components\nof YRA-1909, including chlorogenic acid (CGA), neochlorogenic acid (NCGA), cryptochlorogenic acid\n(CCGA), and their metabolites (i.e., caffeic acid (CA), caffeic acid 3-O-glucuronide (CA-3-G), caffeic\nacid 4-O-glucuronide (CA-4-G), and ferulic acid (FA)) in rat plasma and applied to a pharmacokinetic\nstudy of YRA-1909 in rats. Seven analytes were separated on Halo C18 while using gradient\nelution of formic acid and methanol, and then quantified in selected reaction monitoring mode\nwhle using negative electrospray ionization. Following oral administration of YRA-1909 at doses\nof 25, 50, and 100 mg/kg to male Sprague-Dawley rats, CGA, NCGA, and CCGA were rapidly\nabsorbed and metabolized to CA, CA-3-G, and CA-4-G. The area under the plasma concentration-time\ncurve (AUClast) of CGA, NCGA, CCGA, and three metabolites linearly increased as the YRA-1909\ndose increased. Other pharmacokinetic parameters were comparable among three doses studied.\nAUClast values for CA, CA-3-G, and CA-4-G exceeded those for CGA, NCGA, and CCGA....
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