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Updated: Jun 15, 2026

Spectrophotometric Methods for the Study of Eukaryotic Glycogen Metabolism
Published on: August 19, 2021
A comparison of fetal hemoglobin interference in routine high-performance liquid chromatography, immunoassay, and
Sheila X Soh1, Tze Ping Loh1, Qinde Liu2
1Department of Laboratory Medicine, National University Hospital, Singapore.
Introduction:
Fetal hemoglobin (HbF) is known to cause method-specific interference in glycated hemoglobin A1c (HbA1c) measurement. Data on HbF interference, however, is currently either lacking for some platforms (eg, the Abbott Core Laboratory Alinity c and Beckman Coulter AU5800) or available only for HbF levels lower than the maximum claimed by the manufacturer (eg, Bio-Rad D-100).
Methods:
We examined the effect of HbF interference on 7 HbA1c platforms using a series of spiked adult whole blood samples with increasing HbF levels (0% to 35%) and either low (approximately 5%) or high (approximately 9%) HbA1c levels, using isotope dilution mass spectrometry as a reference measurement procedure.
Results:
For the high-performance liquid chromatography (HPLC)-based platforms (Bio-Rad VARIANT II TURBO 2.0 and D-100), relative deviation from expected values was not clinically significant, even at an HbF level of 35%. In contrast, immunoassay (AU5800; Roche Diagnostics cobas c311 and cobas b101; and Siemens Healthineers DCA Vantage) and enzymatic (Alinity c) methods showed clinically significant deviation at HbF levels above 10%.
Discussion:
Our data suggest that the HPLC methods tested can be used for the majority of patients with elevated HbF. For patients with HbF levels above 10%, immunoassay and enzymatic methods appear to be unsuitable, and alternative HbA1c methods are still advised.

