HPLC analysis of 2-deoxy-D-glucose

What sounds like an unequal David - Goliath battle may be the key to a new therapeutic approach in the fight against COVID-19 disease.

2-deoxy-D-glucose is a glucose molecule in which the hydroxyl group in the 2 position has been replaced by hydrogen.

By inhibiting glycolysis, 2-deoxy-D-glucose affects carbohydrate metabolism and thus could prevent further proliferation of cells infected with the SARS-CoV-2 virus. Recently, the Drugs Controller General of India approved a 2-deoxy-D-glucose based oral drug for emergency use as an adjunct therapy in moderate to severe COVID-19 patients^{(1, 2)}. However, the data from accompanying clinical trials supporting the efficacy of the drug is still incomplete⁽³⁾.
The inhibition of glycolysis by the molecule has also been discussed in tumor therapy to slow down cell growth or induce cell death. Tumor cells exhibit a higher glycolysis rate⁽⁴⁾.

Derivatization was performed with 1-phenyl-3-methyl-5-pyrazolone (PMP).

The reaction of PMP with glucose or other sugars is chemically viewed as a base-catalyzed aldol-addition and condensation between an aldehyde and a ketone. Two PMP molecules become added and serve as UV adsorbing chromophores to increase analytical sensitivity in the subsequent HPLC assay⁽⁵⁾.

The application Fast carbohydrate analysis (MN application No. 127170) shows the HPLC separation of various PMP derivatized sugars in an UV and ESI-iontrap-MS overlay. The multiple endcapped MACHEREY-NAGEL NUCLEODUR C18 Gravity column has been used. As expected, the 2-deoxy-D-glucose with one OH-group less shows a stronger retention behavior on the C18 phase and elutes accordingly late⁽⁶⁾.

Access to application: Fast carbohydrate analysis (MN application No. 127170)

Further examples of drug analysis related to COVID-19

References:
(1) What is 2-deoxy-D-glucose (2-DG) and is it effective against Covid?, The Economic Times, 17 May 2021.
(2) DCGI approves anti-COVID drug developed by DRDO for emergency use". Press Information Bureau, Government of India. 2021-05-08. Retrieved 2021-05-09.
(3) Koshy, Jacob (2021-05-11). "Questions remain on DRDO's COVID drug". The Hindu. ISSN 0971-751X. Retrieved 2021-05-18
(4) Pajak B, Siwiak E, Sołtyka M, Priebe A, Zieliński R, Fokt I, Ziemniak M, Jaśkiewicz A, Borowski R, Domoradzki T, Priebe W. 2-Deoxy-d-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents. Int J Mol Sci. 2019 Dec 29;21(1):234. doi: 10.3390/ijms21010234. PMID: 31905745; PMCID: PMC6982256.
(5) Dr. David Neville, Sugar Molecules in Food (White Paper), https://www.rssl.com.
(6) Rühmann B, Schmidt J, Sieber V, J. Chromatogr. A 1350 (2014) 44 – 50.