title: Development and validation of an ultra-sensitive method for the measurement of plasma renin activity in human plasma via LC-MS/MS.
abstract: BACKGROUND
  Renin catalyzes the conversion of angiotensinogen to angiotensin I (Ang I), the first and rate-limiting step in the renin-angiotensin-aldosterone system. Plasma renin activity (PRA) is an important target engagement biomarker in the clinical development of renin inhibitors. We have developed and validated an improved PRA assay that incorporates an Ang I trapping antibody followed by extraction and quantification of Ang I using a highly sensitive and specific LC-MS/MS method.
  
  
  RESULTS
  The following assay performance characteristics were assessed as part of analytical validation: precision, LOQ, spike recovery, dilution linearity, stability, absolute recovery and biological variability. The assay demonstrated excellent performance characteristics. Notably, the sensitivity of the assay was increased 140-fold when compared with a previous enzyme immunoassay-based assay.
  
  
  CONCLUSIONS
  The improved sensitivity allowed the measurement of >95% PRA inhibition from baseline levels. In addition, we compared the LC-MS/MS-based assay to an enzyme immunoassay-based assay.
authors.affiliation: Clinical Development Laboratory, 126 E Lincoln Avenue, Rahway, NJ 07065, USA.
authors.forename: Derek L
authors.initials: DL
authors.lastname: Chappell
authors.forename: Thomas
authors.initials: T
authors.lastname: McAvoy
authors.forename: Barbra
authors.initials: B
authors.lastname: Weiss
authors.forename: Russell
authors.initials: R
authors.lastname: Weiner
authors.forename: Omar F
authors.initials: OF
authors.lastname: Laterza
mesh_terms: D000803:Angiotensin I / Q000097:blood / Q000276:immunology; D000906:Antibodies / Q000276:immunology; D001774:Blood Chemical Analysis / Q000295:instrumentation / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D012083:Renin / Q000097:blood* / Q000378:metabolism*; D012084:Renin-Angiotensin System; D053719:Tandem Mass Spectrometry
chemical_list: D000906:Antibodies; D000803:Angiotensin I; D012083:Renin