A quantitative LC-MS/MS method for insulin-like growth factor 1 in human plasma

Bronsema, K. J., Klont, F., Schalk, F. B., Bischoff, R., Kema, I. P. & van de Merbel, N. C., Nov-2018, In : Clinical chemistry and laboratory medicine. 56, 11, p. 1905-1912 8 p.

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  • A quantitative LC-MSMS method for insulin-like growth factor 1 in human plasma

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Background: Insulin-like growth factor 1 (IGF1) is a biomarker with various applications in medicine and also in doping control.

Methods: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed that employs 15N-IGF1 as an internal standard. The method features urea-based IGF1/IGFBP-complex dissociation which is directly followed by tryptic digestion. Following solidphase extraction (SPE) sample clean-up of the digest, IGF1 is detected by means of two signature peptides that enable quantification of total IGF1 as well as discrimination between IGF1 proteoforms with 'native' and modified or extended N-terminal sequences.

Results: Our method is capable of measuring plasma IGF1 concentrations over the clinically relevant range of 10-1000 ng/mL and was validated according to regulatory guidelines. Comparison with the IDS-iSYS IGF1 immunoassay revealed good correlation (R-2 > 0.97) and no proportional bias between both assays was observed after normalizing the results against the WHO reference standard for IGF1 (02/254). Evaluation of several commercially available IGF1 preparations showed varying responses which were due to inconsistencies in purity and absolute amount of IGF1 present in these products.

Conclusions: Our LC-MS/MS method introduces urea-based dissociation of IGF1/IGFBP-complexes to enable reliable quantification of IGF1 in plasma. Furthermore, the method is able to detect clinically relevant IGF1 levels without an enrichment procedure at the protein-level and thereby minimizes the risk of losing IGF1 proteoforms during sample preparation.

Original languageEnglish
Pages (from-to)1905-1912
Number of pages8
JournalClinical chemistry and laboratory medicine
Issue number11
Early online date2018
Publication statusPublished - Nov-2018


  • insulin-like growth factor 1 (IGF1), liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), quantification, CHROMATOGRAPHY/TANDEM MASS-SPECTROMETRY, FACTOR-I, GH DEFICIENCY, IGF-I, BIOLOGICAL SAMPLES, HORMONE ABUSE, QUANTIFICATION, PROTEINS, SERUM, PERFORMANCE

ID: 58762713