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

Gwenyth O. Lee, Peter Kosek, Aldo A M Lima, Ravinder Jit Singh, Pablo P. Yori, Maribel P. Olortegui, Jesse L. Lamsam, Domingos B. Oliveira, Richard L. Guerrant, Margaret Kosek

Research output: Contribution to journalArticle

26 Scopus citations


Objectives: 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.

Methods: 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.

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

Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)544-550
Number of pages7
JournalJournal of Pediatric Gastroenterology and Nutrition
Issue number4
StatePublished - Oct 8 2014



  • Environmental enteropathy
  • Intestinal absorption
  • Intestinal permeability
  • Lactulose
  • Mannitol assay
  • Tropical enteropathy

ASJC Scopus subject areas

  • Gastroenterology
  • Pediatrics, Perinatology, and Child Health

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