update

Frontage and Janssen develop preclinical metformin testing method

19-Dec-2011 - Last updated on 20-Dec-2011 at 08:53 GMT

Frontage Laboratories has teamed up with Janssen Pharmaceuticals to develop a chromatographic preclinical testing method they say could finally solve metformin development issues.

The firms say further research on the compound - currently the most prescribed medication for Type II diabetes - has often proved difficult due to its polarity and small size.

However, using a new hydrophilic interaction chromatography tandem mass spectrometry (HILIC-MS/MS) testing method, the researchers hope to side-step current issues of poor retention on reversed-phase liquid chromatographic columns.

The study - published in the next issue of Biomedical Chromatography 2 - adopted a Tecan liquid handling system that allowed researchers to directly inject extracted samples of metformin - dosed together with several experimental drug substances - into rat models.

It achieved acceptable intra-run and inter-run assay precision and more than 99 per cent accuracy over a linear range of 50-5,000 nanograms per millilitre.

Frontage-Janssen say the success of the method is in large part due to this ”high-throughput” capability.

Zhongping (John) Lin, VP of bioanalytical services at Frontage told Outsourcing-Pharma: “This is a big achievement, because previous published metformin methods required additional time consuming evaporation and reconstitution procedures that could lead to potential analyte loss during sample preparation.”

“This direct injection of samples leads to shortened sample preparation and eliminates the potential analyte loss during sample drying down and reconstitution, which in turn increases speed and throughput.”

Growing trend

Frontage and Janssen say their results support the use of hydrophilic interaction chromatography (HILIC) in place of traditional liquid chromatography tandem mass spectrometry (LC-MS/MS).

A spokesperson for the research team, led by Wei Zhang, said of the analysis' advantages over existing methods: "Unlike reversed-phase, organic solvent has weaker elution strength on HILIC."

“Therefore, HILIC also has the advantage of direct injection of extracted samples with high organic concentration generated by protein precipitation, liquid-liquid extraction and solid phase extraction.”