Study On The Bioequivalence Of Sertraline Hydrochloride Capsules And Captopril Tablets

Part 1.Study on the bioequivalence of sertraline hydrochloride capsules by LC/MS/MSSertraline hydrochloride is a type of antidepressant known as a selective serotonin re-uptake inhibitor(SSRI).This type of medicine acts on nerve cells in the brain.In the brain there are numerous different chemical compounds called neurotransmitters.These act as chemical messengers between the nerve cells.Serotonin is one such neurotransmitter and has various functions that we know of.When serotonin is released from nerve cells in the brain it acts to lighten mood.When it is reabsorbed into the nerve cells,it no longer has an effect on mood.It is thought that when depression occurs,there may be a decreased amount of serotonin released from nerve cells in the brain.SSRIs work by preventing serotonin from being reabsorbed back into the nerve cells in the brain. In this way,sertraline helps relieve depression.In order to study sertraline bioequivalence,we establish a LC/MS/MS method for the determination of sertraline in the human plasma.Paroxetine hydrochloride was used as the internal standard.Sertraline was chromatographed by using a Discovery C18 column.The mobile phase consisted of 0.1%formic acide - acetonitrile(50:50).The flow rate was 0.2 mL·min^-1.Electrospray ionization(ESI) source was applied and operated in the positiv ion mode.Selected reaction monitoring(SRM) mode with the transitions of m/z306.0→274.9 and m/z330.1→191.9 were used to quantify sertraline and the internal standard,respectively.The linear calibration curve was obtained in the concentration range of 0.332～66.400ng·L^-1.The limit of quantitation was 0.332±0.002ng·L^-1(n=5).The inter- and intra-day precision(RSD) was less than 9%.The average recoveries were above 95%.The main pharmacokinetics data of referance prepartion and test prepartion(sertraline sulfate capsules):t_maxwere(7.556±2.526) h and(6.889±1.410) h;c_max Were(19.111±5.286) ng·mL^-1 and(19.539±5.311) ng·mL^-1;AUC_0-t were(732.1±251.2) ng·mL^-1·h and(731.9±252.6) ng·mL^-1·h; AUC_0-∞ were(803.4±292.3)ng·mL^-1·h and(795.9±278.1)ng·mL^-1·h.The method was proved to be specific,convenient sample handling,high sensitivity and high accuracy.Test prepartions were found to be bioequivalent to referance preparation.Part 2.Study on the bioequivalence of captopril tablets by LC/MS/MSCaptopril is an ACE(angiotensin converting enzyme) inhibitor.ACE is an enzyme in the body which is important for the formation of angiotensinâ…¡.Angiotensinâ…¡can cause constriction of arteries in the body,thereby cause high blood pressure.ACE inhibitors such as captopril lower blood pressure by inhibiting the formation of angiotensinâ…¡,thus relaxing the arteries.Relaxing the arteries not only lowers blood pressure,but also can improve heart function of patients by improving pumping efficiency of a and cardiac output.Therefore,captopril has been widely used in the clinical treatment of high blood pressure,heart failure and coronary heart disease.Captopril has a weak absorption and has a mercapto in the chemical structural formula.Therefore,captopril is very unstable and it is difficult to detect captopril in the human plasma.For study captopril bioequivalence,we establish a LC/MS/MS method for the determination of captopril in the human plasma.Using p-BPB as a stabilizer and derivative reagent,the derivations were determined by LC-MS/MS using risperidone as the internal standard.Captopril was chromatographed by using a Alltima C₁₈(100 mm×2.1 mm,3.0μm) column.The mobile phase consisted of acetonitrile- 0.025% formic acid solution(60:40).The flow rate was 0.2 mL·min^-1.Electrospray ionization(ESI) source was applied and operated in the positiv ion mode.Selected reaction monitoring(SRM) mode with the transitions of m/z414.1→210.6 and m/z411.3→191.1 were used to quantify captoprii and the intemal standard,respectively.The linear calibration curve was obtained in the concentration range of 1.104～736.000μg·L^-1.The limit of quantitation was 1.104±0.001ng·L^-1(n=5).The inter- and intra-day precision(RSD) was less than 5%.The average recoveries were above 84%.The main pharmacokinetics data of referance prepartion and test prepartion(captopril tablets 12.5mg):t_max were(0.7222±0.1896) h and(0.6806±0.1436) h;c_max were(343.40±132.30) ng·mL^-1 and(333.62±94.60) ng·mL^-1;AUC_0-t were(442.52±95.56) ng·mL^-1·h and(424.86±78.31) ng·mL^-1·h;AUC_0-∞ were(465.30±106.90) ng·mL^-1·h and(449.60±77.76) ng·mL^-1·h.The method was validate to be specific, convenient sample handling,high sensitivity and high accuracy.Test prepartions were found to be bioequivalent to referance preparation.