A novel bedside diagnostic test for methanol poisoning using dry chemistry for formate

Abstract

Background. The standard diagnostic approach to methanol poisoning is chromatographic measurement of methanol on centrally placed stationary equipment. Methanol poisoning in places where such equipment is unavailable is thus often not diagnosed. Methanol is metabolized to a toxic metabolite, formate; the presence of this compound indicates methanol poisoning. We have developed an enzymatic test for formate and modified it into a portable dry chemistry system that could be used anywhere. Methods. The method consists of two enzymatic steps: Formation of NADH from NAD by formate dehydrogenase, and subsequent use of NADH as a reductant of a tetrazolium into a formazan dye that can be quantified photometrically or visually. Results. The photometer gave a good correlation of R² = 0.9893 in serum and R² = 0.9949 in whole blood, showing an instrumental detection limit of less than 1 mM (4.5 mg/dL). The visual readings showed a correlation of R² = 0.8966. Users experienced some difficulty in separating the negative control from the low positives. Conclusions. We have documented the feasibility of an affordable formate strip test for bedside diagnosis of methanol poisoning and for screening of metabolic acidosis of unknown origin. Visual reading is possible, but a reader will improve reliability at lower levels of formate. Future studies are necessary to study the sensitivity and specificity towards other causes of metabolic acidosis and other acids present in human blood.

Key Words::

• Methanol poisoning
• formic acid
• formate dehydrogenase
• acidosis
• diagnosis
• point-of-care technology
• bedside testing

Acknowledgements

This study was supported by an innovation grant from South-Eastern Norway Regional Health Authority. We would like to thank Jan Solberg and Jørund Sollid from Inven2 for the support during the development of this project. We would like to thank Prof. Michael Eddleston, MD, PhD, Edinburgh, Scotland, UK, and Dr Leon Andrew Lane, MD, Oslo University Hospital, Norway for the critical review of the manuscript. The strips are not in commercial production, but it is protected by a patent: If there at any point will be a production and sale of the product, the inventors have given 100% of their share to an ideal fund that will be established to support research and development of treatment options for methanol poisonings, especially in the developing world.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.