title: An automated, high-throughput method for targeted quantification of intact insulin and its therapeutic analogs in human serum or plasma coupling mass spectrometric immunoassay with high resolution and accurate mass detection (MSIA-HR/AM).
abstract: The detection and quantification of insulin and its therapeutic analogs is important for medical, sports doping, and forensic applications. Synthetic variants contain slight sequence variations to affect bioavailability. To reduce sample handling bias, a universal extraction method is required for simultaneous extraction of endogenous and variant insulins with subsequent targeted quantification by LC-MS. A mass spectrometric immunoassay (MSIA), a multiplexed assay for intact insulin and its analogues that couples immunoenrichment with high resolution and accurate mass (HR/AM) spectrometric detection across the clinical range is presented in this report. The assay is sensitive, selective, semi-automated and can potentially be applied to detect new insulin isoforms allowing their further incorporation into second or third generation assays.
authors.affiliation: Thermo Fisher Scientific, BRIMS, Cambridge, MA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Peterman
authors.forename: Eric E
authors.initials: EE
authors.lastname: Niederkofler
authors.forename: David A
authors.initials: DA
authors.lastname: Phillips
authors.forename: Bryan
authors.initials: B
authors.lastname: Krastins
authors.forename: Urban A
authors.initials: UA
authors.lastname: Kiernan
authors.forename: Kemmons A
authors.initials: KA
authors.lastname: Tubbs
authors.forename: Dobrin
authors.initials: D
authors.lastname: Nedelkov
authors.forename: Amol
authors.initials: A
authors.lastname: Prakash
authors.forename: Maryann S
authors.initials: MS
authors.lastname: Vogelsang
authors.forename: Tara
authors.initials: T
authors.lastname: Schoeder
authors.forename: Lewis
authors.initials: L
authors.lastname: Couchman
authors.forename: David R
authors.initials: DR
authors.lastname: Taylor
authors.forename: Cajetan F
authors.initials: CF
authors.lastname: Moniz
authors.forename: Gouri
authors.initials: G
authors.lastname: Vadali
authors.forename: Gregory
authors.initials: G
authors.lastname: Byram
authors.forename: Mary F
authors.initials: MF
authors.lastname: Lopez
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D057166:High-Throughput Screening Assays; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007328:Insulin / Q000031:analogs & derivatives* / Q000097:blood*; D020033:Protein Isoforms; D040901:Proteomics; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D007328:Insulin; D020033:Protein Isoforms
keywords: Diabetes; High resolution accurate mass; Insulin; Mass spectrometry; Targeted assay; Technology