HbA1c analysis by capillary electrophoresis – comparison with chromatography and an immunological method
Open accessAbstract
BACKGROUND: Haemoglobin A1c (HbA1c) has become an even more important analyte for clinical laboratories during recent years with the introduction of its diagnostic use for diabetes mellitus. Several different analytical principles can be used, each with their advantages and disadvantages. AIM: We wanted to compare Sebia Capillarys 2 Flex Piercing (Capillarys) with our routine HbA1c methods, which were an HPLC method (Tosoh G7) and an immunoassay (Tina-Quant on Roche Modular P) by analysing a large clinical material. Furthermore, we investigated sample stability. METHODS: HbA1c analysis was performed in parallel by all three methods for more than 600 patient samples including common and some rare haemoglobin variants, as well as for several controls, some with set target values. Sample stability at room temperature and refrigerated was assessed for up to seven days. RESULTS: Capillarys produced generally somewhat lower HbA1c values than both comparison methods, apparently due to positive bias for the comparison methods. Leaving out samples with haemoglobin variants, we found a mean bias (95% CI) for Capillarys compared to Tosoh G7 (without factorization) and Modular of -0.39 (-0.40 to -0.38) and -0.16 (-0.17 to -0.14) % HbA1c, respectively. HbA1c results were similar between instruments for samples from dialysis patients and for samples with heterozygous common haemoglobin variants, except that Tosoh G7 reported too low results in the presence of Hb E. For heterozygous Hb Raleigh, Capillarys and the immunoassay gave similar results. CONCLUSION: Capillarys is a convenient instrument for routine HbA1c analysis.
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Ion-exchange method and capillary electrophoresis can provide variant information on the result graph, which provides an essential clinical application.
“Notably, ion-exchange method and capillary electrophoresis can provide variant information on the result graph, which provides an essential clinical application (49).”
From Comparison of point‑of‑care HbA1c devices with laboratory HPLC methods: A systematic review and meta‑analysis (2026) · cites this paper as [49]
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“These findings were also in agreement with other studies [32,33,36,37].”
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“In this method, HbA1c is assayed with high precision (less than 2% CVs) [2].”
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Evaluation of interference from 16 hemoglobin variants on hemoglobin A1c measurement by five methods
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“methods based on different analytical principles have been developed for HbA1c assays, such as cation-exchange HPLC, CE, boronate affinity chromatography, and immunoassays [13,14].”
MethodAnalytical performance evaluation of the Norudia HbA1c assay
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“…(HE) is of great importance, but traditional methods of detecting abnormal hemoglobin can lead to certain errors in the test results (8), and some pregnancy complications (such as gestational diabetes, gestational hypertension, etc.) affect the missed screening of HE and reduce the…”
BackgroundKang, F., Li, W., Lou, Y., et al. (2022) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2022.2100822 · Cited by 5 · see citing works
“HbA1c measurement, such as capillary electrophoresis, ionexchange high-performance liquid chromatography (HPLC), immunoassay and enzymatic assays [16,17].”
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“Popular methods to determine HbA1c include cation exchange HPLC, boronate affinity HPLC, capillary electrophoresis, and immunoassays [14,15].”
MethodKhashoggi, H. A., Pignalosa, S., Russo, C., et al. (2018) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2018.1487072 · Cited by 4 · see citing works
“Recent studies described comparison between capillary electrophoresis, chromatography and immunological methods in HbA1c analysis [8,9].”
ResultWei, Y., Gu, M., Ren, Y., & Hu, Z. (2026) · Biomedical Reports · doi:10.3892/br.2026.2120 · Cited by 3 · see citing works
“Notably, ion‑exchange method and capillary electrophoresis can provide variant information on the result graph, which provides an essential clinical application (49).”
Mohamed, S. M., Ramadan, K. S., Saedii, A. A. F., et al. (2024) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-024-01231-x · Cited by 2 · see citing works
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“To date, many methods, such as enzymatic assays [2], capillary electrophoresis [3,4], boronate affinity chromatography [5], ion-exchange high-performance liquid chromatography (ion-exchange HPLC) [6] and immunoassays [7], have been developed and updated.”
MethodStrandberg, J., Gade, I. L., & Hviid, C. V. B. (2024) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2024.2378932 · Cited by 1 · see citing works
“In the present case, assessments were performed utilizing capillary electrophoresis, a technique that is known to be generally resistant to interference [10,11].”
Demirçin, E. Y., Tutar, S., Sezer, S., et al. (2023) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2023.2198145 · Cited by 1 · see citing works
“Separation methods (Ion exchange chromatography, Capillary electrophoresis, Affinity chromatography) and chemical methods (Immunoassays, Enzymatic methods) are common in routine laboratory use [4,5].”
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Glycated albumin and post-transplant diabetes mellitus in kidney transplant recipients
Bleskestad, I. H., Skadberg, Ø., Åsberg, A., & Gøransson, L. G. (2023) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/00045632231152074
“HbA1c was analysed on collection in whole blood with a standardized immunoassay (Tina-Quant on Roche Modular P) until March 2015, and thereafter with a cross-validated capillary electrophoresis method (Sebia Capillarys 2 Flex Piercing).(19) The results were given in % and converted to mmol/mol by using the formula: IF…”
MethodSẮC KÝ LỎNG HIỆU NĂNG CAO VÀ ĐIỆN DI MAO QUẢN TRONG ĐỊNH LƯỢNG HbA1c TRÊN MẪU MÁU BỆNH HEMOGLOBIN
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Hemoglobin Yanase can lead to inaccurate diabetes diagnoses when using HbA1c measurement by HPLC
Parras, P. M., Chamorro, A. M., Reyes, L. R., et al. (2025) · Endocrinología Diabetes y Nutrición (English ed ) · doi:10.1016/j.endien.2026.501716
Belhedi, M., Lazzem, W., Bacha, O., Ba, A., Dabboubi, R., & Chouaieb, S. (2025) · Electrophoresis · doi:10.1002/elps.70064
“%) versus Modular systems, excluding variant samples [ 24 ]. fetal hemoglobin (HbF) caused negative biases proportional to HbF levels [ 30 ].”
Rakotonjafiniarivo, F. H., Rakotomalala, S. M., Antsonantenaina, T., & Ranaivosoa, M. K. (2026) · Cureus · doi:10.7759/cureus.101019 · Cited by 2 · see citing works
“Klingenberg et al. also observed a generally good correlation, showing that immunoturbidimetry follows the general trend of the values provided by HPLC, but the immunological method showed a systematic bias, with a slight underestimation or overestimation depending on HbA1c levels [19].”
Fjeld, B., Jørgensen, M., Lillemoen, P. K. S., et al. (2026) · Hemoglobin · doi:10.1080/03630269.2026.2613682
Self-citationKlingenberg, O., Fjeld, B., & Lundbye, I. B. O. (2026) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2026.2671961
“We analyze HbA1c, also known as glycated hemoglobin, using a Sebia Capillarys 2 FP instrument [10] on a daily basis.”
Self-citationKassid, A. A., & Fawzi, H. A. (2026) · Advances in Redox Research · doi:10.1016/j.arres.2026.100178
Evaluation of HbA1c stability in refrigerated blood samples: for how long are samples fit for use?
Terreni, A., Balboni, F., Paleari, R., Pezzati, P., & Lippi, G. (2026) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2026.2734744
“Similarly, some Authors assessed HbA1c stability at room temperature and under refrigerated conditions for up to 7 days, using capillary electrophoresis, HPLC and immunoassays [6,7].”
Influential
- Authors
- Klingenberg, O., Furuset, T., Hestbråten, C. R., Hallberg, M. H., Steiro, A., Orset, I. R., & Berg, J. P.
- Affiliations
- Oslo University Hospital (NO)
- Corresponding author
- Klingenberg, Olav
- Venue
- Scandinavian Journal of Clinical and Laboratory Investigation
- Publisher
- Informa UK Limited
- Published
- 2017-06-23
- Volume
- 77
- Issue
- 6
- Pages
- 458-464
- ISSN
- 0036-5513 (ISSN-L)
- 1502-7686
- OpenAlex
- W2700133007
- Cited by
- 29
- References
- 11
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 4 · 2020: 4 · 2019: 4 · 2018: 2
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Scandinavian Journal of Clinical and Laboratory Investigation (publishedVersion)
- PubMed (publishedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- HbA1c, capillary electrophoresis, HPLC, immunoassay, method comparison, measurement bias, sample stability, hemoglobin variants, HbE, dialysis patients, diabetes diagnosis
- MeSH terms
- Chromatography, High Pressure Liquid, Glycated Hemoglobin, Humans, Immunoassay, Regression Analysis, Temperature, Electrophoresis, Capillary
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