000			02689 am a22002773u 4500
042			_adc
100	1	0	_aForeman, Rachel E _eauthor
700	1	0	_aMeek, Claire L _eauthor _93117
700	1	0	_aRoberts, Geoffrey P _eauthor _93118
700	1	0	_aGeorge, Amy L _eauthor _93119
700	1	0	_aReimann, Frank _eauthor
700	1	0	_aGribble, Fiona M _eauthor
700	1	0	_aKay, Richard G _eauthor
245	0	0	_aLC-MS/MS based detection of circulating proinsulin derived peptides in patients with altered pancreatic beta cell function
260			_c2022-11-15.
500			_a/pmc/articles/PMC7614196/
500			_a/pubmed/36242807
520			_aRoutine immunoassays for insulin and C-peptide have the potential to cross-react with partially processed proinsulin products, although in healthy patients these are present at such low levels that the interference is insignificant. Elevated concentrations of proinsulin and des-31,32 proinsulin arising from pathological conditions, or injected insulin analogues, however can cause significant assay interferences, complicating interpretation. Clinical diagnosis and management therefore sometimes require methods that can distinguish true insulin and C-peptide from partially processed proinsulin or injected insulin analogues. In this scenario, the high specificity of mass spectrometric analysis offers potential benefit for patient care. A high throughput targeted LC-MS/MS method was developed as a fit for purpose investigation of insulin, insulin analogues, C-peptide and proinsulin processing intermediates in plasma samples from different patient groups. Using calibration standards and bovine insulin as an internal standard, absolute concentrations of insulin and C-peptide were quantified across a nominal human plasma postprandial range and correlated strongly with immunoassay-based measurements. The ability to distinguish between insulin, insulin analogues and proinsulin intermediates in a single extraction is an improvement over existing immunological based techniques, offering the advantage of exact identification of the species being measured. The method promises to aid in the detection of circulating peptides which have previously been overlooked but may interfere with standard insulin and C-peptide immunoassays.
540			_a
540			_ahttps://creativecommons.org/licenses/by/4.0/This work is licensed under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) International license.
546			_aen
690			_aArticle
655	7		_aText _2local
786	0		_nJ Chromatogr B Analyt Technol Biomed Life Sci
856	4	1	_uhttp://dx.doi.org/10.1016/j.jchromb.2022.123482 _zConnect to this object online.
999			_c1004 _d1004