Detection of IGF-1 Protein Variants by Use of LC-MS with High-Resolution Accurate Mass in Routine Clinical Analysis

To the Editor: Low or increased serum insulin-like growth factor 1 (IGF-1)1 concentrations might indicate growth hormone (GH) deficiency or overproduction, respectively. Currently, IGF-1 is mostly measured by automated immunometric assays. However, reagent availability issues prompted us to evaluate LC-MS with high-resolution accurate mass measurement (HRAM) as an alternative (1). We developed and validated an IGF-1 LC-MS HRAM method on a Q Exactive mass spectrometer (Thermo Scientific) using 1:70 000 resolution (at m / z 200) with a mass accuracy of 5 ppm. A similar method has been published for a qTOF instrument (Agilent) (2). We compared our LC-MS-HRAM method initially in 459 patient samples with the iSYS IGF-1 automated immunoassay (IDS). This yielded a least square linear fit of LC-MS HRAM = 0.84 × iSYS + 3.5, with an r 2 of 0.966. During further studies involving 1720 samples to generate reference ranges, the 2 methods continued to be highly correlated, with a reproducible systematic bias. However, we also identified 16 outliers for which the LC-MS HRAM method gave dramatically lower results than the iSYS immunoassay …