title: Development and validation of a reliable and rapid LC-MS/MS method for simultaneous quantification of sacubitril and valsartan in rat plasma and its application to a pharmacokinetic study.
abstract: A selective, sensitive and rapid liquid chromatographic method with electrospray ionization tandem mass spectrometric detection has been developed and validated for simultaneous quantification of sacubitril and valsartan in rat plasma using telmisartan as internal standard (IS). The analytes were extracted by deprotenization of 50 μL of plasma sample using 200 μL of acetonitrile. In a short chromatographic run of 1.50 min run time, separation was achieved on a Hypersil Gold C18 column using a mobile phase composed of 0.1% formic acid in Milli-Q water-0.1% formic acid in acetonitrile in gradient elution mode. The quantification of target compounds was performed in a positive electrospray ionization mode and multiple reaction monitoring. Response was a linear function of concentration in the ranges of 0.5-20,000 ng/mL for both analytes, with r(2)  > 0.9997. The intra- and inter-day precision and accuracy results were <15% and acceptable as per US Food and Drug Administration guidelines. Stability of compounds were established in a battery of stability studies, i.e. bench-top, autosampler and long-term storage stability as well as freeze-thaw cycles. The validated method can be used as a routine method to support pharmacokinetic studies. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: School of Pharmaceutical Sciences and Technologies, Jawaharlal Nehru Technological University, Kakinada, 533 003, Andhra Pradesh, India.
authors.forename: Raja Haranadha Babu
authors.initials: RH
authors.lastname: Chunduri
authors.affiliation: A. U College of Pharmaceutical Sciences, Andhra University, Vishakapatnam, 531 001, Andhra Pradesh, India.
authors.forename: Gowri Sankar
authors.initials: GS
authors.lastname: Dannana
mesh_terms: D000613:Aminobutyrates / Q000097:blood* / Q000493:pharmacokinetics; D047228:Angiotensin II Type 1 Receptor Blockers / Q000097:blood* / Q000493:pharmacokinetics; D057911:Angiotensin Receptor Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D001713:Biphenyl Compounds; D002853:Chromatography, Liquid / Q000379:methods*; D004338:Drug Combinations; D057230:Limit of Detection; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013777:Tetrazoles / Q000097:blood* / Q000493:pharmacokinetics; D000068756:Valsartan / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D000613:Aminobutyrates; D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D004338:Drug Combinations; D013777:Tetrazoles; D000068756:Valsartan; C549068:sacubitril and valsartan sodium hydrate drug combination