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J Pediatr Gastroenterol Nutr. 2014 Oct;59(4):544-50. doi: 10.1097/MPG.0000000000000459.

Lactulose: mannitol diagnostic test by HPLC and LC-MSMS platforms: considerations for field studies of intestinal barrier function and environmental enteropathy.

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  • 1*Department of International Health, Johns Hopkins School of Public Health, Baltimore, MD †Pain Consultants of Oregon, Eugene ‡Department of Physiology and Pharmacology, Federal University of Ceara, Fortaleza, Brazil §Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN ||Asociación Benéfica Proyectos de Informática, Salud, Medicina, y Agricultura (A.B. PRISMA), Iquitos, Peru ¶Center for Global Health and Division of Infectious Disease, University of Virginia, Charlottesville.



The lactulose:mannitol (L:M) diagnostic test is frequently used in field studies of environmental enteropathy (EE); however, heterogeneity in test administration and disaccharide measurement has limited the comparison of results between studies and populations. We aim to assess the agreement between L:M measurement between high-performance liquid chromatography with pulsed amperometric detection (HPLC-PAD) and liquid chromatography-tandem mass spectrometry (LC-MSMS) platforms.


The L:M test was administered in a cohort of Peruvian infants considered at risk for EE. A total of 100 samples were tested for lactulose and mannitol at 3 independent laboratories: 1 running an HPLC-PAD platform and 2 running LC-MSMS platforms. Agreement between the platforms was estimated.


The Spearman correlation between the 2 LC-MSMS platforms was high (ρ ≥ 0.89) for mannitol, lactulose, and the L:M ratio. The correlation between the HPLC-PAD platform and LC-MSMS platform was ρ = 0.95 for mannitol, ρ = 0.70 for lactulose, and ρ = 0.43 for the L:M ratio. In addition, the HPLC-PAD platform overestimated the lowest disaccharide concentrations to the greatest degree.


Given the large analyte concentration range, the improved accuracy of LC-MSMS has important consequences for the assessment of lactulose and mannitol following oral administration in populations at risk for EE. We recommend that researchers wishing to implement a dual-sugar test as part of a study of EE use an LC-MSMS platform to optimize the accuracy of results and increase comparability between studies.

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