Interlaboratory Agreement of Insulin-like Growth Factor 1 Concentrations Measured by Mass Spectrometry

Abstract

BACKGROUND:Insulin-like growth factor 1 (IGF-1) 7 is a key mediator of growth hormone (GH) action and a well-characterized biomarker of GH abuse. Current immunoassays for IGF-1 suffer from poor concordance between platforms, which makes comparison of results between laboratories difficult. Although previous work has demonstrated good interlaboratory imprecision of LC-MS/MS methods when plasma is supplemented with purified proteins, the interlaboratory imprecision of an endogenous protein in the nanogram-per-milliliter concentration range has not been reported.

Pitfalls of Insulin-like Growth Factor-I and Growth Hormone Assays

“…Measurements by mass spectrometry in 5 different laboratories correlated better: r 2 5 0.78 to 0.87 for healthy individuals and r 2 5 0.78 to 0.88 for patients with acromegaly. 44 The authors stated that the method of calibration was the major source of variation in the mass spectrometry study. They did not speculate with reasons for the interlaboratory differences seen with the automated immunoassay, but the 2 laboratories were using different assay and calibrator lots, which could have contributed to the observed discrepancy.…”

Targeted mass spectrometry analysis of the proteins IGF1, IGF2, IBP2, IBP3 and A2GL by blood protein precipitation

“…Their quantification is typically achieved independently by classical methods such as ELISA or RIA assays [18], necessitating blood sample volumes that range between 50 and 200 μL for each assay. Specific LC-MS/MS methods have been recently developed for plasma/ serum samples for quantification of IGF1 [25] and IGF1 and A2GL [19] by protein precipitation, and of IGF1 by specific antibody-based purification [26], necessitating 100 μL, 30 μL and 40 μL, respectively. In this manuscript, we describe a sensitive and scalable method for the quantification of all five proteins by protein precipitation and selected reaction monitoring (SRM) LC-MS/MS analysis [27], requiring a total of 7 μL of plasma, and reaching a throughput of up to 80 analyses per day.…”

Impact of the Choice of IGF-I Assay and Normative Dataset on the Diagnosis and Treatment of Growth Hormone Deficiency in Children

“…Analysis of IGF-I with mass spectrometry can circumvent some of the problems that are inherent to immunoassays, e.g., interference of IGF-binding proteins or cross-reactivity of IGF-II [29, 30]. Mass spectrometry might be a promising technique to reduce variability in IGF-I analysis and to improve standardization across platforms, provided that calibration procedures are harmonized [31]. The development of a robust IGF-I reference method is clinically relevant and should be the focus of future research.…”