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‐C 18 (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.