Determination of radical yields in solid-state drugs as one technique to identify drugs that will withstand radiosterilization: radioresistance of beta blockers.
This article describes a simple preliminary test to determine whether a drug is sufficiently radioresistant to withstand radiosterilization. The test is based on the electron spin resonance (ESR) detection of radicals produced after irradiation of a solid-state drug, assuming that these radicals are the precursors of the final products detected after dissolution of the drug. A calibration curve has therefore been established by measuring ESR spectra of l-alanine irradiated at different doses. The response factor to quantify the radicals is the normalized double integration (DI) of the whole first-derivative ESR spectrum. The curve gives the relationship between the normalized DI and the number of radicals. Eight beta blockers have been chosen and their radical yield determined. This is the first time that several different drugs of the same pharmacological group have been studied and compared. The results obtained are similar for seven of the eight beta blockers; the mean G value (excepted for nadolol) is 3 x 10(-9) mol/J. This means that beta blockers are radioresistant. The two most radiosensitive drugs (nadolol and esmolol hydrochloride) were also studied by high-performance liquid chromatography (HPLC). No significant loss of the active compound was detected, which confirms this radioresistant property. Moreover, no change in color or smell was observed. Using ESR and HPLC, beta blockers were identified as potential candidates for radiosterilization.
Engalytcheff
Alix
A
Laboratory of Chemical and Physicochemical Analysis of Drugs (CHAM), School of Pharmacy, Université Catholique de Louvain, Brussels, Belgium. alix.engalytcheff@cham.ucl.ac.be
Deridder
Véronique
V
Debuyst
René
R
Tilquin
Bernard
B
D000319:Adrenergic beta-Antagonists / Q000528:radiation effects*; D000409:Alanine / Q000737:chemistry; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D004351:Drug Resistance; D004578:Electron Spin Resonance Spectroscopy; D008872:Microwaves; D008956:Models, Chemical; D009248:Nadolol / Q000528:radiation effects; D004364:Pharmaceutical Preparations / Q000528:radiation effects; D011412:Propanolamines / Q000528:radiation effects; D013242:Sterilization / Q000379:methods*; D013696:Temperature
D000319:Adrenergic beta-Antagonists; D004364:Pharmaceutical Preparations; D011412:Propanolamines; D009248:Nadolol; C036604:esmolol; D000409:Alanine