HPLC Detection and Quantification of Radiolytic Products of Eight  -Blockers Irradiated in the Solid State and Hypotheses on Their Origins

Engalytcheff, Alix; Vanhelleputte, Jean-Paul; Tilquin, Bernard

doi:10.1023/b:pham.0000032995.57881.79

Cited by 6 publications

(5 citation statements)

References 14 publications

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“…If a breakage of that bond occurs, the resulting radicals recombine almost completely so that no final products resulting from this breakage are detected. This observation may support a previous hypothesis that final products may not originate directly from radicals (6,10). If final products were directly related to radicals, radicals centered on the nitrogen (loss of the ethyl), on the benzylic carbon (loss of chlorine), and on the carbon adjacent to the nitrogen (loss of the methyl) should also be observed by ESR.…”

Section: Link Between Radicals and Final Productssupporting

confidence: 87%

“…For these, radiolytic products are generally present in such low amounts that very sensitive techniques are required for their analysis (6,7). Up to now, many studies were devoted to the determination of radicals trapped in the solid matrix, but few have been performed on final products and on the mechanism leading to their formation (8,9).…”

Section: Introductionmentioning

confidence: 99%

“…Up to now, many studies were devoted to the determination of radicals trapped in the solid matrix, but few have been performed on final products and on the mechanism leading to their formation (8,9). As past studies have shown that no direct correlation may be established between trapped radicals and final products (6,10), electron spin resonance (ESR) studies should be considered as an additional method to detect irradiated drugs, as is the case of irradiated foods (11). Therefore, only chromatographic techniques are suited to determine the radiostability of a drug.…”

Section: Introductionmentioning

confidence: 99%

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Electron Beam and Gamma Radiolysis of Solid-State Metoclopramide

et al. 2006

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Section: Link Between Radicals and Final Productssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Electron Beam and Gamma Radiolysis of Solid-State Metoclopramide

et al. 2006

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“…The effect of gamma irradiation in the dose of 30 kGy on nadolol has been studied by a Belgian group (Engalytcheff et al 2003(Engalytcheff et al , 2004. For analysis of the effect, they used the electron paramagnetic resonance (EPR) to evaluate the concentration of free radicals and ultra-high performance liquid chromatography (UHPLC) to detect the radiolysis products.…”

Section: Introductionmentioning

confidence: 99%

Radiodegradation of nadolol in the solid state and identification of its radiolysis products by UHPLC–MS method

et al. 2017

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Nadolol ((2R*,3S*)-5-{[(2R*)-3-(tert-butylamino)-2-hydroxypropyl]oxy}-1,2,3,4 tetrahydronaphthalene-2,3-diol) in substantia was exposed to ionizing radiation generated by a beam of high-energy electrons in an accelerator, in the standard sterilisation dose of 25 kGy and in higher doses of 50 -400 kGy. The irradiated and non-irradiated (control) samples were analysed by the infrared spectrophotometry, electron paramagnetic resonance, differential scanning calorimetry (DSC) and ultrahigh performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). The irradiated samples were found to contain free radicals in concentrations much higher than that observed for the other irradiated b-blockers. On the basis of UHPLC-MS results, it was possible to establish structures of 11 compounds of the impurities and/ or products of nadolol decomposition. The main product of radiodegradation was concluded to be formed as a result of abstraction of the hydroxyl group and aromatization of the tetrahydronaphthalene ring. The results of DSC measurements confirmed the presence of radiolysis products in the irradiated samples of nadolol. A shift of the endothermic peak corresponding to melting towards lower temperatures (by 4.4°C at the dose of 400 kGy) was directly proportional to the doses of radiation used, which permits concluding that this method is sensitive and suitable for evaluation of radiodegradation of nadolol in solid phase.

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“…To make such a verification a given drug should be irradiated with high doses of ionising radiation (γ, β, E-beam) whose effect should be tested by a number of analytical methods (chromatographic, spectrometric, thermal) permitting evaluation of radiochemical stability of a given drug, allowing observation of all kinds of changes and identification of the products of radiolysis [8][9][10] . Radiochemical stability of MT has been studied by other authors [11][12][13][14] , but the studies mainly concerned the influence of ionising radiation on water solutions of MT. In water solutions MT undergoes radiolysis after such a small dose of irradiation as 12.8 kGy.…”

Section: Introductionmentioning

confidence: 99%

The effect of ionizing radiation on metoprolol

Ogrodowczyk

Marciniec

Czwajda

2012

Drug Development and Industrial Pharmacy

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The influence of ionising radiation on physico-chemical properties of metoprolol tartrate (MT) in solid phase was studied. The compound was irradiated by radiation produced by a beam of high-energy electrons in an accelerator, in doses from 25 to 400 kGy, and the possible changes in the samples were detected by organoleptic analysis (colour, forms, clarity), chromatographic and spectrometric methods. Already at the standard sterilisation dose of 25 kGy, the presence of free radicals (0.3764 × 10(16) spin/g) and a decrease in the melting point by 1°C were noted. At higher doses of irradiation products of radiolysis appeared (100 kGy) and the colour was changed from white to pale cream (200 kGy). Our observation was that with increasing mass loss of MT after irradiation with 100, 200 and 400 kGy, the concentration of free radicals increased from 1.0330 to 1.6869 × 10(16) spin/g. The radiolytic yield of total radiolysis was 4.54 × 10(7) mol/J for 100 kGy, 7.42 × 10(7) mol/J for 200 kGy and 4.74 × 10(7) mol/J for 400 kGy. No significant changes were observed in the character of FT-IR spectra, but in UV an increase in intensity of the band at the analytical wavelength was noted. As follows from the results MT shows high radiochemical stability for the typical sterilisation doses 25-50 kGy, and will probably be able to be sterilised by radiation in the dose of 25 kGy.

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HPLC Detection and Quantification of Radiolytic Products of Eight -Blockers Irradiated in the Solid State and Hypotheses on Their Origins

Cited by 6 publications

References 14 publications

Electron Beam and Gamma Radiolysis of Solid-State Metoclopramide

Electron Beam and Gamma Radiolysis of Solid-State Metoclopramide

Radiodegradation of nadolol in the solid state and identification of its radiolysis products by UHPLC–MS method

The effect of ionizing radiation on metoprolol

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