Tetrahydrofuran also is much slower to equilibrate with the column and LC system than is acetonitrile or methanol - it may take twice the solvent volume for initial equilibration with tetrahydrofuran. And, of course, tetrahydrofuran s unpleasant odor is another negative factor. However, I would not argue with anyone who preferred methanol as a starting solvent. If the samples are neutral compounds, you may be able to use water as the aqueous phase. However, ionic compounds generally are present in pharmaceutical analysis and many other applications.
Ionic compounds require analysts to maintain pH control to obtain reproducible methods.
You will get the best results if the compounds are fully protonated or fully ionized. For organic acids, working at pHs lower than pH 3 generally will be satisfactory. However, bases will require buffers with pHs higher than pH 8, which exceeds the recommended working pH of most silica-based columns. Silica columns with extended pH ranges are available now, but few have extensive experience with these materials at high pH, so I recommend organic buffers to reduce silica dissolution. These factors make me wary of routine use of high-pH mobile phases with silica columns.