Abstract
Measurement of insulin-like growth factor-1 (IGF-I) has utility for the diagnosis and management of growth disorders, but inter-assay comparison of results has been complicated by a multitude of reference standards, antibodies, detection methods, and pre-analytical preparation strategies. We developed a quantitative LC-MS method for intact IGF-I, which has advantages in throughput and complexity when compared to mass spectrometric approaches that rely on stable isotope dilution analysis of tryptic peptides. Since the method makes use of full-scan data, the assay was easily extended to provide quantitative measurement of IGF-II using the same assay protocol. The validated LC-MS assay for IGF-I and IGF-II provides accurate results across the pediatric and adult reference range and is suitable for clinical use.
Highlights
The anabolic activity of insulin-like growth factor-1 (IGF-I) and its role in childhood growth have been extensively investigated, and quantitative analysis of IGF-I has been an essential tool in the diagnosis and treatment of human growth disorders since its measurement in serum became widely available [1]
The use of IGF-I as a diagnostic tool for growth disorders is complicated by inter-assay variability that may arise from differences in antibody specificity, pre-analytical sample preparation strategies to remove binding protein interferences, noncommutability of calibration material, and dynamic range of the detection methodology [1,2,3]
From a technical perspective several key considerations are required for clinically useful determination of IGF-I: excellent precision and accuracy, within and at the extremes of normal physiological ranges; and freedom from interferences primarily considered to be associated with the presence of IGF binding proteins (IGFBPs) [4]
Summary
The anabolic activity of insulin-like growth factor-1 (IGF-I) and its role in childhood growth have been extensively investigated, and quantitative analysis of IGF-I has been an essential tool in the diagnosis and treatment of human growth disorders since its measurement in serum became widely available [1]. The use of IGF-I as a diagnostic tool for growth disorders is complicated by inter-assay variability that may arise from differences in antibody specificity, pre-analytical sample preparation strategies to remove binding protein interferences, noncommutability of calibration material, and dynamic range of the detection methodology [1,2,3]. From a technical perspective several key considerations are required for clinically useful determination of IGF-I: excellent precision and accuracy, within and at the extremes of normal physiological ranges; and freedom from interferences primarily considered to be associated with the presence of IGF binding proteins (IGFBPs) [4]. While IGF-II is affected by the presence of IGFBPs, the analytical demands are somewhat less given the dramatically higher circulating levels and relatively minor changes as a function of gender and age
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