Synchronized determination of sacubitril and valsartan with some co-administered drugs in human plasma via UPLC-MS/MS method using solid-phase extraction.
An accurate and sensitive UPLC-MS/MS method was developed and validated for the simultaneous estimation of the newly developed combination of sacubitril and valsartan and the co-administered drugs nebivolol, chlorthalidone and esomeprazole in human plasma. Solid-phase extraction was conducted for the purification and extraction of the drugs from human plasma. Chromatographic separation was carried out on an Agilent SB-C18 (1.8 μm, 2.1 × 50 mm) column using losartan as internal standard. Isocratic elution was applied using acetonitrile-0.1% formic acid in water (85: 15, v/v) as mobile phase. Detection was carried out using a triple-quadrupole tandem mass spectrometer using multiple reaction monitoring, at positive mode at m/z 412.23 → 266.19 for sacubitril, m/z 436.29 → 235.19 for valsartan, m/z 405.8 → 150.98 for nebivolol, m/z 346.09 → 198 for esomeprazole and a selected combination of two fragments m/z 423.19 → 207.14 and 423.19 → 192.2 for losartan (internal standard), and in negative ionization mode at m/z 337.02 → 190.12 for chlorthalidone. The method was linear over the concentration ranges 30-2,000 ng/ml for sacubitril, 70-2,000 ng/ml for valsartan, esomeprazole and chlorthalidone and 70-5,000 pg/ml for nebivolol. The developed method is sensitive and selective and could be applied for dose adjustment, bioavailability and drug-drug interaction studies.
['Moussa|Bahia Abbas|BA|', 'Hashem|Hanaa M A|HMA|', 'Mahrouse|Marianne Alphonse|MA|', 'Mahmoud|Sally Tarek|ST|https://orcid.org/0000-0001-8741-8271']
D000613:Aminobutyrates D001713:Biphenyl Compounds D002752:Chlorthalidone D002851:Chromatography, High Pressure Liquid D004338:Drug Combinations D004355:Drug Stability D064098:Esomeprazole D006801:Humans D057230:Limit of Detection D016014:Linear Models D000068577:Nebivolol D015203:Reproducibility of Results D052616:Solid Phase Extraction D053719:Tandem Mass Spectrometry D000068756:Valsartan
sacubitril valsartan solid-phase extraction nebivolol chlorthalidone esomeprazole