CPSA 2011
Science and Technology Coming Together to Make a Difference
October 3 - 6, 2011
Bucks County Sheraton Hotel
Langhorne, PA
Poster Abstract #18
A Sensitive Assay for the Measurement of Endogenous Levels of Angiotensin Peptides as a Biomarker Utilizing HPLC-MS/MS Detection
GlaxoSmithKline Pharmaceuticals Bioanalytical Science and Toxicokinetics, PTS DMPK King of Prussia, PA USA
Angiotensin is a potent vasoconstrictor. When circulating in the body Angiotensin I is converted to Angiotensin II by cleavage of the dipeptide histidine-Leucine from the C-terminus of Angiotensin I by the Angiotensin converting enzyme (ACE). Angiotensin II is converted to Ang 1-7 by Angiotensin converting enzyme 2 (ACE2) which is further broken down to Ang 1-5.
A method for the determination of Ang II, Ang 1-7 and Ang1-5 was developed using LC-MS/MS and a one run validation was successful for the range of 5 to 1000 pg/mL for Angiotensin II and 1 -7 and 10 to 1000 pg/mL for Angiotensin 1-5. All precision and bias values were +/- 20% which meets acceptance criteria. Angiotensin II and 1-7 were quantitated to support two toxicology studies which provided critical biomarker data for the project. The method is sensitive, selective and robust which successfully analyzed in vivo study samples