| Pain brings patients strongly painful feeling,and the drug therapy in clinical is a most effective way for the treatment of pain in a short time.Strong analgesic drugs are morphine and sauteralgyletc and so on,but the side effects of these drugs is large and can't be used frequently.Meptazinol hydrochloride,as a new analgesic drug,has little dependence and high safety.In order to investigate the effects of dose,food and sex on the absorption rate and extent of meptazinol hydrochloride tablets in vivo,reduce the cost of listing capsules and study on the metabolite of this drug.In this paper,it has developed liquid chromatography–mass spectrometry methods to analyze the concentration of meptazinol hydrochloride and its metabolites in plasma,and then application on the bioequivalence,the pharmacokinetics and the metabolites about the drug.the specific researched contents are as follows:The plasma sample with isotopic internal standard was separated on C18 column using gradient elution with a mobile phase of acetonitrile(B)–water(A)containing 5 mM ammonium acetate and 0.05%formic acid,and The flow rate was set at 0.40 mL/min,and the injection volume of 20?L,and the mass transition ion-pair of m/z 234.2?107.1(meptazinol hydrochloride)and m/z 237.3?107.1(IS)was used for the quantitative detection,then developing a liquid chromatography–mass spectrometry method to analyze the concentration of meptazinol hydrochloride.The method was validated in the linear range of 1.26~224 ng/mL,and the result showed that the method had a good specificity and was not interfered with by endogenous substances such as amino acids,and The linear correlation coefficient of the standard curve was 0.9995.The RSD of the matrix was 2.50%~8.80%and the accuracy was 90.99%~105.11%.The recovery rate was86.46%~91.26%.The matrix effect RSD was 2.13%~2.49%,and the RSD of stability was 0.10%~7.00%.All the above validated indexes meet the requirements of biological analysis.Therefore,this method was suitable for the determination of meptazinol hydrochloride in plasma samples treated with methanol precipitation protein.Then,based on the measured drug concentration,the correlation of the main pharmacokinetic parameters with the dose,the influence of sex and food,and the tendency of accumulation in the body were analyzed by using the related statistical software.At the same time,it was also possible to evaluate the equivalent of meptazinolhydrochloride tablets and capsules in vivo.In the MS mode,using the electrospray ionization(ESI)and selective ion detection(MRM),as well as 500?ion source temperature,60 V desorption voltage(DP),40 Psi curtain gas(CUR),40 psi atomization gas and 50 Psi of auxiliary gas,and the metabolites in plasma of meptazinol hydrochloride could be identified.When the mass ratio of the fragment ions([M+H]~+)was 248.2,250.3 and 220.2 in the mass spectrum of plasma sample,these indicated that 7-oxomeptazinol,3-hydroxyethylmeptazinol and N-desmethylmeptazinol were the three major phase I metabolites.Otherwise,it also found several phase II metabolites acidified by glucuronic acid and sulfuric acid.A LC-MS/MS method was developed for simultaneous dermination of metabolites in plasma treated with enzymatic and protein precipitation,and then from the curve of the average concentration with time could be seen that changed trend for analytes in vivo was basically same. |
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