Determination of valproic acid in human plasma by LC-MS/MS method / 国际检验医学杂志

Objective To develop a rapid and sensitive liquid chromatography-tandem mass spectrometric(LC-MS/MS) method for the determination of valproic acid in human plasma.Methods After treating human plasma sample by acetonitrile protein precipitation method,the analytes were separated on a Shimpack VP-ODS analytical column(150 mm×2.0 mm I.D,5 μm) with the mobile phase of methanol and 5 mmol/L ammonium acetate (55∶45,v/v)at a flow rate of 0.4 mL/min.Detection was carried out by adopting the multiple reaction monitoring(MRM) scanning mode in the API3200 triple quadrupole tandem mass spectrometer,electrospray ionization source,negative ion mode,selected monitoring ionic reactions were m/z 142.9→m/z 142.9(valproic acid) and m/z 179.0→m/z 179.0(1-sulfonic acid).Results Valproic acid and internal standard 1-sulfonic acid retention time were 3.03 min and 2.38 min respectively.The plasma valproic acid linear range was 0.800-80.0 μg/mL(r>0.99) with the lower limit of quantitation(LLOQ) 0.800 μg/mL.The intra-and inter-batch relative standard deviations(RSD) were both less than 15%,and the relative errors(RE) were within ±15%.The mean extraction recovery rate was(84.1±2.4)%,and the mean matrix effect factor was(104.3±2.0)%.In the stability study,valproic acid was found to be stable in plasma under various storage conditions.Conclusion This method is suitable for the determination of valproic acid in human plasma and human pharmacokinetic study of valproic acid semisodium sustained release tablet.

Regulation of lovastatin on a key inflammation-related microRNA in myocardial cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Advances in the understanding of cardiovascular pathogenesis have highlighted that inflammation plays a central role in atherosclerotic coronary heart disease. Therefore, exploring pharmacologically based anti-inflammatory treatments to be used in cardiovascular therapeutics is worthwhile to promote the discovery of novel ways of treating cardiovascular disorders.</p><p><b>METHODS</b>The myocardial cell line H9c2(2-1) was exposed to lipopolysaccharide (LPS) in culture and resulted in a cellular pro-inflammation status. miR-21 microRNA levels were detected using quantitative real-time polymerase chain reaction (Q-RT-PCR). The influence of lovastatin on miR-21 under normal and pro-inflammatory conditions was tested after being added to the cell culture mixture for 24 hours. Conditional gene function of two predicted cardiovascular system relevant downstream targets of miR-21, protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and signal transducer and activator of transcription 3 (STAT3), were analyzed with immunoblotting.</p><p><b>RESULTS</b>Forty-eight hours of LPS treatment significantly increased the miR-21 to 170.71%± 34.32% of control levels (P = 0.002). Co-treatment with lovastatin for 24 hours before harvesting attenuated the up-regulation of miR-21 (P = 0.013). Twenty-four hours of lovastatin exposure up-regulated PPP1R3A to 143.85%± 21.89% of control levels in cardiomyocytes (P = 0.023). Lovastatin up-regulated the phosphorylation level of STAT3 compared to the background LPS pretreatment (P = 0.0077), this effect was significantly (P = 0.018) blunted when miR-21 was functionally inhibited.</p><p><b>CONCLUSIONS</b>miR-21 plays a major role in the regulation of the cellular anti-inflammation effects of lovastatin.</p>

Pharmacokinetics of ibuprofen enantiomers in rats after intravenous and oral administration of ibuprofen arginate / 药学学报

The pharmacokinetics of ibuprofen enantiomers were studied in rats after intravenous and oral administration of ibuprofen arginate by means of a chiral HPLC method. The pharmacokinetics of ibuprofen was stereoselective after intravenous and oral administration of ibuprofen arginate. The pharmacokinetic stereoselectivity was higher after oral administration than that after intravenous administration. The systematic (R)-(-)-to-(S)-(+) inversion might be more important than the presystematic one in the stereoselective pharmacokinetics after oral administration. Oral administration of ibuprofen arginate resulted in a very rapid absorption of (S)-(+)-ibuprofen (eutomer), and the absolute bioavailabilities of (S)-(+)-ibuprofen and (R)-(-)-ibuprofen were about 100% and 80%, respectively. Based on the systemic exposure of (S)-(+)-ibuprofen, it could be concluded that the pharmacological actions might be similar when ibuprofen arginate was given orally and intravenously, except some differences in the onset of action.

Determination of alfuzosin in Human Serum by HPLC / 中国药房

OBJECTIVE:Alfuzosin concentration in human serum was determined by RP-HPLC METHODS:The mobile phase was methanol-acetonitrile-phosphate buffer-triethylamine(10∶30∶60∶0 05) After being extracted with ethyl ace_tate,alfuzosin was analyzed by reversed-phase HPLC (Shim-pack CLC-ODS,4 6mm?150mm,5?m)and fluorescence detection with excitation wavelength set at 334nm and emission at 378nm RESULTS:Over the concentration range of 0 4～51 2?g/L,the linear regression equation was A=0 3 909C+0 0 605(n=8,r=0 9 996) The average recovery of alfuzosin was 99 4% The intra-and inter-day RSDs were less than 15% CONCLUSION:The method is accurate and can be used for studying the pharmacokinetics of alfuzosin

Protective effect of Silybin Capsules on hepatic injury induced by combining isoniazid with rifampin in mice / 中成药

Objective: To observe the protective effect of Silybin Capsules (SC) on mice hepatic toxic injury induced by isonicotinic acid hydrazide (INH) and rifampin (RFP) when used in combination Methods: The serum level of ALT, liver index, contents of glutathion (GSH) and malondialdehyde (MDA), activity of microsomal cytochrome P450 and its isoform P4502E1 in liver were measured. Results: SC obviously inhibited the rising of liver index, serum ALT, liver MDA and the activity of microsomal cytochrom P450 and its isoform P4502E1, and increased the liver GSH. Histopathological examination showed that Silibinin Capsules evidently alleviated the condition of the degeneration of hepatic cells and that of necrosis. Conclusion: The protective effect of SC on mice hepatic injury induced by both IIVit and RFP may be related to stabilizing the liver membrane, inhibiting the the lipid peroxidation, scavenging the free radical and decreasing the activity drug metabolizing enzyme.