Issue 1265, 1981

Polarographic study of flurazepam and its major metabolites

Abstract

The polarographic behaviours of flurazepam, N-1-hydroxyethylflurazepam, flurazepam-N-1-acetic acid, N-1-desalkylflurazepam and N-1-desalkyl-3-hydroxyflurazepam have been systematically studied over the pH range 0–14. Values for pK1 and pK3, obtained from a study of E½versus pH and i1im.versus pH relationships, corresponding to protonation of the azomethine group and deprotonation of the hydrogen ion attached to the nitrogen atom in position I, respectively, have been determined and are in agreement with those obtained by more accurate spectrophotometric methods. Values of pK2 corresponding to protonation of the nitrogen atom in the diethylamino side-chain in the first of the above compounds, the carboxylic acid function in the third and the 3-hydroxy function in the last, inaccessible by spectrophotometric methods, have been determined polarographically as 9, 4.5 and 5.5, respectively.

Linear calibration graphs of ipversus concentration in pH 4 formate buffer were obtained down to 5 × 10–8M using cathode-ray and differential-pulse polargraphy and were linear over a least three orders of magnitude of concentration for flurazepam and the metabolites listed above. Capsules containing 15 and 30 mg of active constituent were assayed by a method involving cathode-ray polarography and relative standard deviations in the range 0.66–2.66% were obtained.

Article information

Article type
Paper

Analyst, 1981,106, 890-897

Polarographic study of flurazepam and its major metabolites

J. A. Groves and W. F. Smyth, Analyst, 1981, 106, 890 DOI: 10.1039/AN9810600890

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