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2017 ; 89
(11
): 6188-6195
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Assuring Consistent Performance of an Insulin-Like Growth Factor 1
MALDImmunoassay by Monitoring Measurement Quality Indicators
#MMPMID28467045
Klont F
; Ten Hacken NHT
; Horvatovich P
; Bakker SJL
; Bischoff R
Anal Chem
2017[Jun]; 89
(11
): 6188-6195
PMID28467045
show ga
Analytical methods based on mass spectrometry (MS) have been successfully applied
in biomarker discovery studies, while the role of MS in translating biomarker
candidates to clinical diagnostics is less pronounced. MALDImmunoassays-methods
that combine immunoaffinity enrichment with matrix-assisted laser desorption
ionization time-of-flight (MALDI-TOF) mass spectrometric detection-are attractive
analytical approaches for large-scale sample analysis by virtue of their ease of
operation and high-throughput capabilities. Despite this fact, MALDImmunoassays
are not widely used in clinical diagnostics, which is mainly due to the limited
availability of internal standards that can adequately correct for variability in
sample preparation and the MALDI process itself. Here we present a novel
MALDImmunoassay for quantification of insulin-like growth factor 1 (IGF1) in
human plasma. Reliable IGF1 quantification in the range of 10-1000 ng/mL was
achieved by employing (15)N-IGF1 as internal standard, which proved to be an
essential feature of the IGF1 MALDImmunoassay. The method was validated according
to U.S. Food and Drug Administration (FDA) guidelines, which included
demonstrating the effectiveness of IGF1/IGF binding protein (IGF1/IGFBP) complex
dissociation using sodium dodecyl sulfate (SDS). Furthermore, the MALDImmunoassay
compared well with the IDS-iSYS IGF1 immunoassay with high correlation (R(2) =
0.99), although substantially lower levels were reported by the MALDImmunoassay.
The method was tested on >1000 samples from a cohort of renal transplant
recipients to assess its performance in a clinical setting. On the basis of this
study, we identified readouts to monitor the quality of the measurements. Our
work shows that MALDI-TOF mass spectrometry is suitable for quantitative
biomarker analysis provided that an appropriate internal standard is used and
that readouts are monitored to assess the quality of the measurements.