Problem in the analysis of sodium valproate

[Tequila]

Dear members of this forum,

I need your opinions in order to solve an analytical problem. I am working with the dissolution test of sodium valproate tablets and my problem is chromatographic purely not the dissolution method.
In the test, the solution test is 0.002 % w/v, the volume injected is 50 uL, the wavelength of measuring is 220 nm and the solvent is buffer pH 6.8 (the mobile phase is 60 % buffer pH 6.8 and 40 % acetonitrile). In this conditions the area was very small and I have to change the conditions in order to increase the area and I reach about 300 mAu*min with a symmetry factor of about 0.75 when the European pharmacopoeia limit is 0.8.
The conditions of working was 100 uL, 210 nm and the concentration was 200 mg/L. In my opinion the fronting is owing to a high concentration injected but the drug had a very low absorbance. The initial test is a British pharmacopoeia method which I had to change. I worked with a diluent less strong than the mobile phase which minimize the overlad (buffer pH 6.. The original column uBondapack C18 and I worked with Lichrospher C18 but the particle size is 5 um in both columns.
I will appreciate your opinions in order to get better results, Thanks in advance for your help,

Diego

[Uwe Neue]

Fronting is not commonly caused by column overload, but by other details in the procedure. Thus could the pH of the sample (you are working at a mobile phase of pH 7, and dissolution methods are commonly carried out at a rather acidic pH) or other related things such as the sample solvent. If it is the pH, a diluting of the sample with your mobile phase buffer will solve the problem.

The problem could also be related to other details of the method setup that you needed to vary because you did not use the originally recommended column.

[vimal]

Sodium valproate as such is very soluble in water.As for my knowledge the BP/EP method uses GC only for its analysis of related substances.Though the sample concentration of 200 ppm is reasonable, the diluent and the mobile phase should be suitable enough to determine the valproic acid present in the sample.pH 3.0 in both the mobile phase and the sample diluent with phenyl column can be tried.