Analytical validation of a MALDI-TOF mass spectrometry method for serum IGF-1 measurement and its comparison with...

Insulin-like growth factor 1 (IGF-1) is an important biomarker in the diagnosis and monitoring of growth hormone-related disorders. MALDI-TOF mass spectrometry has potential for high-throughput IGF-1 measurement, but its analytical performance for routine clinical application requires systematic validation.

Analytical performance of a MALDI-TOF MS-based IGF-1 assay was evaluated following CLSI guidelines, including imprecision, accuracy, linearity, limit of quantitation (LOQ), analytical specificity, sample stability, and sample type comparison. Method comparison was performed against LC-MS/MS and CLIA using 287 patient serum samples.

Intra-assay coefficients of variation (CVs) were 3.66% and 1.82% at low (26.52 ng/mL) and high (375.49 ng/mL) concentrations, respectively; inter-assay CVs were 6.21% and 3.21%. The assay was linear (r = 0.998) with an LOQ of 5 ng/mL. Recoveries ranged from 87.70% to 91.73%. Cross-reactivity with IGF-2 and insulin was negligible. Serum IGF-1 remained stable for 3 days at 25°C, 9 days at 2-8°C, and 12 weeks at -20°C, and tolerated five freeze-thaw cycles. EDTA plasma and serum showed acceptable agreement (mean bias 0.36%-6.62%) for interchangeable use. Method comparison showed strong correlations: MALDI-TOF MS vs. LC-MS/MS (Passing-Bablok: Y = -5.602 + 0.746X, r = 0.996) and vs. CLIA (Y = 2.378 + 0.739X, r = 0.994).

The MALDI-TOF MS method achieved acceptable analytical performance for serum IGF-1 measurement, including precision, linearity, stability, and specificity. The observed systematic bias relative to LC-MS/MS and CLIA suggests that method-specific reference intervals are needed. MALDI-TOF MS is a reliable and high-throughput alternative for clinical IGF-1 testing.