Inter-Laboratory Agreement of Insulin-like Growth Factor 1 Concentrations Measured Intact by Mass Spectrometry

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 66; no. 4; pp. 579 - 586
• Main Authors: Moncrieffe, Danielle, Cox, Holly D, Carletta, Samantha, Becker, Jessica O, Thomas, Andreas, Eichner, Daniel, Ahrens, Brian, Thevis, Mario, Bowers, Larry D, Cowan, David A, Hoofnagle, Andrew N
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.04.2020; American Association for Clinical Chemistry, Inc
• Subjects: Digestion; Equipment and supplies; Growth factors; Growth hormone; Growth hormones; Human growth hormone; Immunoassay; Immunoassays; Insulin; Insulin-like growth factor I; Insulin-like growth factors; Laboratories; Laboratory equipment; Mass spectrometry; Mass spectroscopy; Measurement; Measuring instruments; Samples; Somatotropin; Statistical analysis; Statistical methods; Trypsin; United Kingdom; Intact protein LC-MS; Anti-Doping; Inter-laboratory; Growth Hormone; Insulin Growth Factor 1
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1093/clinchem/hvaa043

Abstract Background Insulin-like growth factor-I (IGF-1) is measured mainly by immunoassay for the diagnosis and treatment of growth hormone (GH) disorders, and to detect misuse of GH in sport. Immunoassays often have insufficient inter-laboratory agreement, especially between commercial kits. Over the expected range of IGF-1 in blood (∼50–500 ng/mL), in an inter-laboratory study we previously established a measurement imprecision of 11% (%CV) for the digested protein analyzed by LC-MS. Measuring intact IGF-1 by LC-MS should be simpler. However, no inter-laboratory agreement has been published. Methods Intact and trypsin-digested IGF-1 in 32 serum samples from healthy volunteers and human growth hormone administration studies were analyzed by LC-MS using different instruments in five laboratories, as well as by immunoassay in a single laboratory. Another 100 samples were analyzed for IGF-1, both intact and after trypsin-digestion, in each laboratory by LC-MS. The statistical relationship between measurements and the imprecision of each assay group was assessed. Results An intra-laboratory variability of 2-4% CV was obtained. Inter-laboratory variability was greater at 14.5% CV. Orthogonal regression of intact versus trypsin-digestion methods (n = 646) gave a slope of 1.01 and intercept of 2.05 ng/mL. Conclusions LC-MS measurements of IGF-1 by intact and trypsin-digestion methods are not statistically different and each is similar to immunoassay. The two LC-MS approaches may be used interchangeably or together to eliminate concerns regarding an immunoassay IGF-1 measurement. Because intact and digested IGF-1 measurements generally agreed within 20% of each other, we propose this as a criterion of assay acceptability.