Simultaneous determination of indapamide,perindopril and perindoprilat in human plasma or whole blood by UPLC-MS/MS and its pharmacokinetic application

Simple and sensitive methods were developed for the determination of indapamide, perindopril and its active metabolite perindoprilat in human plasma or whole blood by hyphenated ultra-performance li- quid chromatography-mass spectrometry （UPLC-MS/MS）. lndapamide-d3, perindopril-d4 and perindoprilat-d4 were used as the internal standards. The separation was performed on a Thermo BDS Hypersil C18 column （4.6 mm × 100 mm, 2.4 μm） for indapamide and perindopril simultaneously following a protein precipitation pretreatment of the biosamples. The separation of perindoprilat was achieved independently on a phenomenex PFP column （4.6 mm × 150 mm, 5 μm）. All the analytes were quantitated with positive electrospray ionization and multiple reactions monitoring mode. The assay exhibited a linear range of 1-250 ng/mL for indapamide, 0.4-100 ng/mL for perindopril and 0.2-20 ng/mL for perindoprilat. The methods were fully validated to meet the requirements for bioassay in accuracy, precision, recovery, reproducibility, stabilities and matrix effects, and successfully applied to the pharmacokinetic study of perindopril tert-butylamine/indapamide compound tablets in Chinese healthy volunteers and the comparative pharmacokinetic study between plasma and whole blood.

Enalapril Combined with Hydrochlorothiazide and Indapamide in the Treatment of Hypertension with Heart Failure

Objecrive:To explore the effect of enalapril combined with hydroch1orothiazide and indapamide on hypertension and heart failure.Methods:8o patients with hypertension and heart failure admitted to our hospitail from January 2019 to January 2020 were selected as the research subjects,and they were divided into two groups with random number table method,40 cases each.The control group was given conventional treatment regimens,including enalapril and hydroch1orothiazide;the observation group replaced hydrochlorothiazide with indapamide based on the above therapies.The efficacy and systolic blood pressure,diastolic blood pressure and left heart ejection fraction(LVEF)of the two groups were compared.Results:After treatment,the effective rate of the observation group was 92.50%(37/40)higher than that of the control group 75.00%(30/40).The systolic and diastolic blood pressure were lower than those of the control group,and the LVEF was higher than that of the control group.The difference was statistically significant(P<0.05).Conclusion:Enalapril combined with indapamide is effective in the treatment of hypertension with heart failure,which can help 1ower blood pressure,reduce heart 1oad,increase cardiac output,reverse ventricular remodeling,and delay disease progression.

Simultaneous Analysis of Indapamide and Related Impurities in Sustained-Release Tablets by a Single-Run HPLC-PDA Method

The contents of indapamide and related impurities in generic indapamide sustained-release tablets were simultaneously detected by a single-run high performance liquid chromatography equipped with photodiode array detector(HPLC-PDA)method for the quality control in this paper.The results showed the method had a good selectivity and was validated through linearity,limits of detection and quantification,recovery,and precision.The linear ranges of indapamide,2-methyl-1-nitroso-2,3-dihydro-1H-indole(impurity A,ImA),4-chloro-N-(2-methyl-1H-indol-1-yl)-3-sulphamoyl-benzamide(impurity B,ImB)and 4-chloro-3-sulfamoylbenzoic acid(impurity 1,Im1)were 0.028-1.80μg/mL(R=0.99995),0.060-1.20μg/mL(R=0.9996),0.0324-1.20μg/mL(R=0.99985)and 0.060-1.20μg/mL(R=0.9997)with detection limits of 0.0093,0.012,0.012 and 0.006μg/mL,respectively.ImA and Im1 were not detectable in the generic drug.The content of indapamide was 96.7%of the labeled amount with a relative standard deviation(RSD)of 1.30%,and the percentage of ImB relative to the labeled amounts of indapamide was 0.106%with an RSD of 1.82%.The content of other unspecified impurities all met the reference quality standards.The results provided references for the quality control and the quality standard study of generic indapamide sustained-release tablets.