RESUMEN
A stable HMG-CoA reductase (HMGR) reaction in vitro was developed by a sensitive, selective and precise liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. The optimized enzyme reac-tion condition contained 1.5μg of HMGR, 20 nM of NADPH with 50 min of reaction time. The method was validated by several intra-and inter-day assays. The production transitions of m/z 147.0/59.1 and m/z 154.0/59.1 were used to detect and quantify mevalonolactone (MVAL) and MVAL-D7, respectively. The accuracy and precision of the method were evaluated over the concentration range of 0.005–1.000μg/mL for MVAL and 0.010–0.500μg/mL for lovastatin acid in three validation batch runs. The lower limit of quantitation was found to be 0.005μg/mL for MVAL and 0.010μg/mL for lovastatin acid. Intra-day and inter-day precision ranged from 0.95%to 2.39%and 2.26%to 3.38%for MVAL, 1.46%to 3.89%and 0.57% to 5.10% for lovastatin acid, respectively. The results showed that the active ingredients in Xuezhikang capsules were 12.2 and 14.5 mg/g, respectively. This assay method could be successfully applied to the quality control study of Xuezhikang capsule for the first time.
RESUMEN
OBJECTIVE Toillustratethepharmacokineticsandpharmacodynamicsofdifferentdos-agesofsustained-releaseimplantofgoserelininrats.METHODS Theratsreceivedasingledoseof sustaineed-release i mplant of goserelin 0.3,0.6 and 1 .2 mg per rat by subcutaneous injection,respec-tively.Concentrations of goserelin and testosterone in plas ma were determined by HPLC-MS/MS.The pharmacokineticparameterswerecalculatedbyWinNonlin6.3.RESULTS Themainpharmacokinetic parameters of the 0.3,0.6 and 1 .2 mg per rat were as fowllows:the area under the concentration-time curve(AUC0-t)was 770 ±96,1534 ±299 and (3233 ±777)μg·L-1·h,and the maximum plasma con-centration(cmax)was 3.7 ±0.3,6.8 ±2.2 and (1 7.6 ±5.4)μg·L-1 ,respectively.Regression analysis was applied to analyze the relationship between AUC0-t and cmax at different doses and those relative coefficients were 0.942 and 0.923 respectively.AUC0-t and cmax increased with the dose in the range of 0.3-1 .2 mg per rat.As for other main pharmacokinetic parameters (peak time,half life,mean resi-dence time,clearance and apparent volume of distribution),there was no significant difference between the three groups.Testosterone plasma concentration reached the highest level following administration and then kept decreasing to low concentrations.Between 28 d and 35 d,testosterone plas ma concentra-tionslowlyincreasedtothenormallevel.CONCLUSION Pharmacokineticcharacteristicsofsustained-release implant of goserelin in rats show a linear relationship,within the dose range of 0.3-1 .2 mg per rat.The results from pharmacodynamic data show that testosterone does not change in a dose-depend-ent manner at a dose ranging from 0.3 to 1 .2 mg per rat.Testosterone plasma concentration decreases to theoretical castrate level (0.5 μg·L-1 )after 4 d following a dose of 0.6-1 .2 mg per rat.