| Autor: |
Orive, Maria M., Gallo, Blanca, Alonso, Rosa M., Vicente, Francisca, Viré, Jean C., Patriarche, Gaston J. |
| Zdroj: |
Microchimica Acta; May 1989, Vol. 97 Issue: 3-4 p181-190, 10p |
| Abstrakt: |
The acid-base behaviour of midazolam, a psychotropic drug derived from imidazobenzodiazepine family, has been studied spectro-photometrically. This compound hydrolyzes at pH values lower than 4. Reversible cleavage of the azomethine bond takes place and the open-ring compound is in equilibrium with the closed-ring compound (protonated form of the parent drug). Absorbance-time data (measured at 225 nm and for different pH values) have been evaluated by a pseudo-first order logarithmic approach, leading to different apparent kinetic constants, depending on pH and temperature. A simple mechanism of hydrolysis, corresponding to fast protonation and slow hydrolysis with opening of the ring is in good agreement with the kinetic results. From data obtained at pH values greater than 4, the deprotonation constant of the nitrogen atom at position 2 of the imidazole ring has been calculated and a pKa value of 5.50 ± 0.05 obtained. In addition, a Spectrophotometric method has been developed which allows the determination of midazolam at concentrations from 1.23 × 10-6M to 3.38 × 10-5M. This method has been applied to a pharmaceutical formulation midazolam; the Dormicum error, in terms of relative standard deviation, was lower than 1.5%. |
| Databáze: |
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