Different dilution solvent, different peak area?

[danko]

No, it is not Hilic.
It is a regular RP method, utilizing 80% Methanol and 20% Water………
…………….The analyte was very hydrophilic and hence no solubility issues.

A very hydrophilic analyte would usually point towards some kind of NP/HILIC. And 80% ACN fits quite well in that picture.
Besides, inconsistent peak areas do not exactly indicate “strong solventâ€

[HW Mueller]

Well, it appears, then, that mohan didn´t have some mysterious problem, but probably the same one justin has: Low solubility of analyte in water. In mohan´s case it´s especially plausible: The high MeOH system had fairly hydrophobic analyte(s), hence low solubility in water and variable amts injected. The lower MeOH system´s analytes were soluble enough in water to be quite robust regarding the amount solvated and injected.
We are apparently wrecking our brains about a trivial problem.

[Tomasz]

justo

It looks like your API has better solubility in your dissolution medium than in water. The dissolution medium is probably 0,1 N HCl or 0,1 N HCl with SDS. Probably low pH (0,1 N HCl) or addition of SDS results in much higher solubility of your API in the dissolution medium than in water. Making dilution in water you also lower the concentration of this co-solubilizer. This can result in precipitation of you API. Try making dilution in your dissolution medium.