Detection of the radiolysis of solid ampicillin by UV - spectroscopy

We propose to detect the use of g-rays in order to radiosterilize ampicillin by UV absorption spectroscopy. The UV absorption results are verified by comparison with HPLC-diode array analysis. The sensitivity is excellent ($10^{-6}$ M). The wavelengths in the range from 287 to 335 nm are characteristics of radiolysis related substances. It is possible to use this range of wavelengths to detect the radiolysis of ampicillin with an usual UV spectrophotometer.

Étude RPE de médicaments «ionisés» et «photolysés»

La Résonnance Paramagnétique Electronique (R.P.E.) est la technique la plus adaptée pour la mise en évidence de l'irradiation gamma subie par un médicament à stériliser ou à décontaminer. Toutefois, certains composés peuvent produire des radicaux piégés détectables par R.P.E. suite à une exposition à des rayonnements ultraviolets

Détection RPE de l'irradiation de médicaments

Le spectre R.P.E. de radicaux piégés dans des antibiotiques solides irradiés pourrait permettre la détection d'une radiostérilisation. En effet le signal R.P.E. n'est détecté qu’après radiolyse et, à température ambiante, peut être observé dans certains cas pendant plusieurs années. La constante de vitesse des réactions radicalaires de métathèse peut être rapide ou très lente, le chemin réactionnel n'est pas connu

[Esr Study of Irradiated and Photolyzed Drugs]

Trapped radicals are used to detect the sterilization of solid drugs by gamma rays. However, some drugs present trapped radicals after U.V. irradiation. The quantitative E.S.R. measurements are different between U.V. photolysis and gamma radiolysis

Radiolyse et radiostérilisation des médicaments

L'ionisation des aliments n'induit pas de risque toxicologique si la dose délivrée n'est pas supérieure à 10 kGy. La tendance est d'étendre cette règle aux substances médicamenteuses irradiées. Toutefois, les médicaments "ionisés" doivent satisfaire aux exigences de la Pharmacopée. L'expérience du chloramphénicol irradié montre que, pour la dose de stérilisation (15 à 25 kGy), le médicament irradié satisfait à la plupart des tests de pureté. Toutefois, ces tests n'ont pas été mis au point pour la détection d'éventuels produits caractéristiques de la radiolyse. Une détection chromatographique pourrait être utilisée pour les substances radio-sensibles, comme des antibiotiques de type B-lactame, mais exigerait une ré-irradiation

A new validation approach applied to the GC determination of impurities in organic solvents

Organic solvents such as methanol, acetone, dichloromethane or toluene are frequently used in the pharmaceutical industry. The manufacturing of new active pharmaceutical ingredients (APIs) under GMP conditions commands to control adequately the quality of the different ingredients happening in the synthesis. Organic solvents have therefore to be controlled and their purity has to be determined before any GMP synthesis. A selective gas chromatography (GC) method has been developed to determine the purity of acetone, dichloromethane, methanol and toluene. Using this method, the main contaminants of each organic solvent can be quantified. Moreover, the developed method allows the simultaneous determination of ethanol, isopropanol, chloroform, benzene, acetone, dichloromethane, methanol and toluene. Propionitrile was used as the internal standard. The separation was obtained on a CP-SIL 8-CB low bleed/MS column (60 m x 0.32 mm, i.d. x 1.0 mu m coating thickness). The GC method was fully validated using a new approach based on the accuracy profile as a decision tool. The determination of P-expectation tolerance intervals for the estimation of total error - including both bias and precision - is used to better reflect the actual performances of the method, which is definitively the objective of the validation. The different validation criteria such as selectivity, response function, trueness, precision, accuracy, linearity or limits of detection and quantification were considered. The method was found to be able to quantitate with a good accuracy impurities around the 0.1 % (v/v) concentration level for the different solvents. (c) 2005 Elsevier B.V. All rights reserved

Electron spin resonance studies of some irradiated pharmaceuticals

Five antibiotics belonging to the cephalosporins and penicillins groups have been irradiated: anhydrous ampicilline acid, amoxicilline acid trihydrate, cefuroxime sodium salt, cloxacilline sodium salt monohydrate and ceftazidime pentahydrate. ESR studies have been carried out, showing the influence of irradiation and storage parameters on the nature and concentration of the free radicals trapped. These results may be used to detect an irradiation treatment on such pharmaceuticals. (C) 2000 Elsevier Science Ltd. All rights reserved

[Esr Measurements and the Detection of Radiosterilization of Drugs]

The ESR spectrum of trapped radicals in irradiated solid antibiotics could permit the detection of the radiosterilization. The ESR signal is detected only after radiolysis; at room temperature, this ESR spectrum is observable for a few hours or until several years. The rate of the metathesis reactions can be fast or very slow, the reaction path is unknown. However, in many cases, the polycrystalline solid phase exhibits its ability to keep radicals for a long period of time and the detection of the radiolysis is possible during this period

Comparison of liquid chromatography and capillary electrophoresis methods for quantification of sodium residuals

Liquid chromatography (LC) and capillary electrophoresis (CE) methods were developed to perform the determination of residual sodium in mother liquors and successive washes of an active pharmaceutical ingredient (API). The addition of sodium chloride to the product solution results in rapid and complete crystallization of the API. The LC method was coupled to evaporative light scattering detection (ELSD) while the CE approach was based on indirect UV detection. Both methods were fully validated. Selectivity, response function, trueness, precision, accuracy, linearity and limits of detection (LOD) and quantification (LOQ) were the criteria investigated. The LC-ELSD method was found to be more sensitive than the CE/indirect UV approach. The methods were found to be valid over concentration ranges of 62-500 and 235-1500 ppm for the LC and the CE methods, respectively. Both methods were compared and used for the determination of actual samples coming from different batches of the same API chemical synthesis. (c) 2006 Elsevier B.V. All rights reserved