ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

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

Magdalena Ogrodowczyk, Katarzyna Dettlaff, Waldemar Bednarski, Barbara Ćwiertnia, Maciej Stawny, Grzegorz Spólnik, Juliusz Adamski, and Witold Danikiewicz

Poznan University of Medical Sciences, Poznań, Poland

E-mail: mogrodo@ump.edu.pl

Abstract: 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 ultra-high 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 β-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.

Keywords: Nadolol ; Radiosterilization ; Free radicals ; Degradation product ; UHPLC–MS 

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-017-0284-7

Chemical Papers 72 (2) 349–357 (2018)