Solubility and acid-base behaviour of midazolam in media of different pH, studied by ultraviolet spectrophotometry with multicomponent software

J Pharm Biomed Anal. 1991;9(6):451-5. doi: 10.1016/0731-7085(91)80246-6.


The solubility of midazolam is less than 0.1 mg ml-1 at neutral pH and it increases considerably in acidic media. A pKa value of 6.04 at 24 +/- 1 degree C was calculated from the solubility data. In acidic media midazolam is reversibly converted to the corresponding benzophenone (open-ring form). The extent of this reaction was investigated by assaying the two compounds simultaneously by UV spectrophotometry with multicomponent software. The structure of the benzophenone derivative was verified by IR, MS and 1H and 13C NMR spectrometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, Thin Layer
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Midazolam / chemistry*
  • Software
  • Solubility
  • Spectrophotometry, Ultraviolet


  • Midazolam