Spectroscopic analysis of pindolol irradiated in the solid state

Pindolol ((2RS)-(1-(1H-indol-4-iloxy)-3- [(1-metyloetylo)amino]-2-propanol) in substantia was exposed to ionising radiation emitted by high energy electrons from an accelerator, in the standard sterilisation dose of 25 kGy and in higher doses from the range 50–400 kGy. The effects of irradiation were checked by spectrometric methods (UV, MS, FT-IR, EPR) and hyphenated methods (HPLC-MS) and the results were referred to those obtained for non-irradiated sample. EPR results indicated the presence of free radicals in irradiated samples, in the amount of 1.36 × 10¹⁶ spin g^?1 for 25 kGy and 3.70×10¹⁶ spin g^?1 for 400 kGy. The loss of pindolol content determined by HPLC was 1.34% after irradiation with 400 kGy, while the radiolytic yield of the total radiolysis for this dose of irradiation was 2.69×10⁷ mol J^?1. By means of HPLC-MS it was possible to separate and identify one product of radiolytic decomposition, which probably is 2-((R)-3-(1H-indol-4-yloxy)-2-hydroxypropylamino)propan-1-ol formed upon oxidation. In the range of sterilisation doses (25–50 kGy), pindolol was found to show high radiochemical stability and would probably be safely sterilised by the standard dose of 25 kGy.      

DSC and spectroscopic studies of disulfiram radiostability in the solid state

The effect of ionising radiation on the physico-chemical properties of disulfiram (Antabuse, Esperal, bisdiethylthiocarbamoil disulphide) has been studied by DSC, FTIR, EPR, MS, TLC and HPLC. Sterilisation was carried out in the solid state, at room temperature and normal air humidity using the electron beam of 9.96 Mev from accelerator. All the measurements were made simultaneously for the irradiated and nonirradiated substance. It has been found that the drug studied in solid phase when subjected to an electron beam corresponding to the irradiation in the doses 10–100 kGy shows the presence of free radicals (EPR), and a change in colour from white to pale green-grey that disappears after solution in water or methanol. After the irradiation with the dose of 100 kGy, its melting point and enthalpy slightly decreased. Also the content of the active substance decreases (HPLC −1.5%, UV −3.6%, iodometric titration method −2.7%) and trace amounts of the radiolysis products appear (HPLC). The substance irradiated with the doses 10–50 kGy does not show changes in the melting point, in the content and presence of the radiolysis products. The EPR results have shown that free radicals disappear after about a year and the discolouring disappears with them. The results of this study have shown that disulfiram can be subjected to sterilisation by irradiation with no deterioration of its physico-chemical properties, but a long time of storage needed to remove free radicals and discolouration questions the economic justification for this type of sterilisation.     

Analytical study on irradiated methylxanthine derivatives

The effect of ionising radiation on the physico-chemical properties of three derivatives of xanthine: caffeine, theophylline and theobromine, has been studied. The above-drugs in the solid phase have been irradiated with E-beam of the energy 9.96 MeV with the doses varied from 25 to 400 kGy. The effects of the irradiation have been examined by differential scanning calorimetry (DSC), electron paramagnetic resonance (EPR) and high-performance liquid chromatography (HPLC). The results have shown that the methylxanthine derivatives studied are resistant to ionising irradiation in the doses usually used for sterilisation (<50 kGy), which means that they are relatively radiochemically stable and can be sterilised by irradiation.     

DSC study of radiostability of 1,4-dihydropyridine derivatives

The effect of sterilisation by irradiation has been studied for the seven most often used in medicine derivatives of 1,4-dihydropyridine (nifedipine, nisoldipine, nicardipine, nitrendipine, nimodipine, felodipine and amlodipine). The sterilisation was performed for the compounds in the solid phase with an electron beam of the energy 10 MeV, at room temperature, using the irradiation doses from 20 to 400 kGy. The effects of the irradiation were studied by the methods SEM, DSC, XRD and TLC. The sterilisation with doses 20-100 kGy was found to cause no changes in the physico-chemical properties of the compounds, while the irradiation with higher doses (200-400 kGy) was found to induce changes in the colour, DSC spectrum and TLC picture. As follows from the TLC results, the main product of radiolysis of the compounds studied was a pyridine nitrozoderivative, which indicates the same mechanism of decomposition as in the process of photodegradation. The results prove that the 1,4-dihydropyridine derivatives being highly sensitive to visible and UV radiation are generally resistant to ionising radiation and thus can be subjected to sterilisation by irradiation. This revised version was published online in July 2006 with corrections to the Cover Date.     

Thermal study of four irradiated imidazoline derivatives in solid state

Four imidazoline derivatives: antazoline (AN), naphazoline (NN), tymazoline (TM), xylometazoline (XM), in the form of hydrochlorides in solid phase have been subjected to high energy e-beam irradiation from an accelerator (~10 MeV) at a dose varied from 25 to 200 kGy. The effects of the irradiation have been assessed by DSC, X-ray diffraction, FTIR, EPR and TLC. The standard sterilisation dose of 25 kGy has been found to produce changes in the properties of one derivative (XM), two other ones (AN and TM) have been found sensitive to doses >100 kGy, whereas NN has been resistant to irradiation in the whole range studied (25–200 kGy). EPR results indicated that the changes taking place in the therapeutic substances studied are related to radical formation. The irradiation induced changes in colour, a decrease or increase in the melting point, changes in the XRD pattern, small changes in the shape of FTIR peaks and the presence of radiolysis products. The XM compounds cannot be sterilised by irradiation because of the radiation induced changes in its physico-chemical properties.     

Challenges in validating the sterilisation dose for processed human amniotic membranes

Most of the tissue banks in the Asia Pacific region have been using ionising radiation at 25 kGy to sterilise human tissues for save clinical usage. Under tissue banking quality system, any dose employed for sterilisation has to be validated and the validation exercise has to be a part of quality document. Tissue grafts, unlike medical items, are not produced in large number per each processing batch and tissues relatively have a different microbial population. A Code of Practice established by the International Atomic Energy Agency (IAEA) in 2004 offers several validation methods using smaller number of samples compared to ISO 11137 (1995), which is meant for medical products. The methods emphasise on bioburden determination, followed by sterility test on samples after they were exposed to verification dose for attaining of sterility assurance level (SAL) of 10⁻¹. This paper describes our experience in using the IAEA Code of Practice in conducting the validation exercise for substantiating 25 kGy as sterilisation dose for both air-dried amnion and those preserved in 99% glycerol.     

Thermal and spectroscopic analysis of florfenicol irradiated in the solid-state

The study has been undertaken to check the effect of ionising radiation on the physical and chemical properties of florfenicol, an antibiotic of a wide range of antibacterial activity. The solid-state samples were subjected to an electron beam generated by accelerator corresponding to the doses of 25, 100 and 400 kGy, and the effect of the exposure was analysed by the methods not requiring changes in the state (with no preliminary treatment), such as SEM, DSC, FTIR, XRD, EPR and HPLC. Florfenicol irradiated with a dose of 25 kGy has not changed the form or colour, however, a small increase in intensity of some absorption bands in the FTIR spectrum and of some peaks in the XRD pattern, a decrease in the melting point by 0.6°C, the appearance of free radicals and a loss in the FF content within the error of the method (0.91%) have been observed. After irradiation with greater doses (100 and 400 kGy) the changes have intensified, yellow discolouration appeared and the loss of FF content has increased to 6.39%. As follows from the results, the compound studied in solid-state undergoes radiolysis after e-beam irradiation in the doses ≥25 kGy, but lower doses (15–20 kGy) can be applied for its decontamination or sterilization with no adverse effect on its physico-chemical properties.     

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

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.     

Solid state radiolysis of sulphur-containing amino acids: cysteine,cystine and methionine

The sulphur-containing proteinaceous amino acids l-cysteine, l-cystine and l-methionine were irradiated in the solid state to a dose of 3.2 MGy. This dose corresponds to that delivered by radionuclide decay in a timescale of 1.05 × 10⁹ years to the organic matter buried at a depth >20 m in comets and asteroids. The purity of the sulphur-containing amino acids was studied by differential scanning calorimetry (DSC) before and after the solid state radiolysis and the preservation of the chirality after the radiolysis was studied by chirooptical methods (optical rotatory dispersion, ORD) and by FT-IR spectroscopy. Although the high radiation dose of 3.2 MGy delivered, all the amino acids studied show a high radiation resistance. The best radiation resistance was offered by l-cysteine. The radiolysis of l-cysteine leads to the formation of l-cystine. The radiation resistance of l-methionine is not at the level of l-cysteine but also l-methionine is able to survive the dose of 3.2 MGy. Furthermore in all cases examined the preservation of chirality after radiolysis was clearly observed by the ORD spectroscopy although a certain level of radioracemization was measured in all cases. The radioracemization is minimal in the case of l-cysteine and is more pronounced in the case of l-methionine. In conclusion, the study shows that the sulphur-containing amino acids can survive for 1.05 × 10⁹ years and, after extrapolation of the data, even to the age of the Solar System i.e. to 4.6 × 10⁹ years.     

Neutron bombardment of lithium bis(oxalato) borate: LiBOB

Lithium bis(oxalato) borate (LiBOB) was neutron bombarded with a flux of 2.40 × 10¹² n cm⁻² s⁻¹ for 1, 2, 3 and 4 h. The neutron damaged LiBOB was studied by FT-IR and Raman spectroscopy as well as by DSC (Differential Scanning Calorimetry). It is shown that the neutron bombardment causes the radiolysis of the oxalate ligand of LiBOB producing boric acid. The kinetics of LiBOB radiolysis under neutron bombardment was fitted according to the pseudofirst order kinetics law using either the FT-IR data or the decomposition enthalpy data leading in both cases to a rate constant of 9.2 × 10⁻⁵ s⁻¹. Pristine LiBOB is not a paramagnetic solid but after neutron bombardement it gives a very clear and stable ESR signal attributed to trapped spins in the radiolysis products.

     

The influence of radiation sterilization on thiamphenicol

The effect of ionising radiation, applied in the form of an electron beam, in the doses of 25, 100 and 400 kGy on the physical and chemical properties of thiamphenicol in solid phase has been studied by organoleptic analysis (form, colour, smell, solubility, clarity) and spectroscopic methods (UV, IR, EPR), chromatography (TLC), SEM observations, X-ray diffraction, polarimetry and thermal method (DSC). The above-discussed results have proved that on irradiation with a dose of 25 kGy no significant changes appear in thiamphenicol, apart from the formation of free radicals of the lifetime of over 352 days. On irradiation with much higher doses (100 and 400 kGy) no changes were observed in the IR spectra but the UV line intensities slightly increased at lambda(max)=266 and 273 nm, the colour of the powder changed, the radiolysis products appeared as detected by TLC, changes were also observed in the XRD, SEM pictures, the melting point values (DSC) and optical rotation. On the basis of DSC results a linear relation was found between the irradiation dose and the decrease in the melting point and increase in the enthalpy of melting, characterised by high correlation coefficients of r=0.9839 and 0.9622, respectively. Moreover, a linear relation was established between the optical rotation angle and the irradiation dose, alpha(D) ( degrees )=f(dose), characterised by the correlation coefficient r=0.9874. The results obtained indicate that thiamphenicol can be safely subjected to radiation sterilization by the standard dose of 25 kGy.     

Hydrogen yield from water radiolysis in the presence of zeolites

This paper reports a study of the decomposition of water by gamma radiolysis in the presence of zeolites ZSM-5, SAPO-5, and MOR. The irradiation is performed using ⁶⁰Co as a source with 1.12×10¹⁵ Bq activity at a 8.3 kGy/h dose rate. The stable products of radiolysis as well as the other chemical species are measured by mass spectrometry. The calculated radiation yield (G_{H 2}) generally decreases in the order: H-ZSM-5>Na-ZSM-5>H-SAPO-5>MOR under the given experimental conditions; the yield is higher in the presence of these catalysts than in their absence.     

High energy induced decoloration and mineralization of Reactive Red 120 dye in aqueous solution: A steady state and pulse radiolysis study

Gamma radiation induced decoloration and degradation of aqueous solution of Reactive Red 120 dye (RR-120) have been investigated under different experimental conditions. Rate constants for the reaction of hydrated electron and hydroxyl radical with RR-120 were determined to be 1.2×10¹⁰ and 7.9×10⁹ mol^?1 dm³ s^?1, respectively, by pulse radiolysis technique. The decoloration and degradation efficiency were measured in terms of % decoloration and % TOC, respectively. Decoloration was observed to be most efficient under reducing condition, where the radiolytic yield for the decoloration of dye was determined to be 0.14 μmol/J. The extent of decoloration for both aerated and oxygen saturated solution was almost identical, whereas it decreased in N₂O saturated solution as well as N₂ saturated solution. For a solution having 10.56 μg/ml total organic carbon (TOC) at a dose of 3 kGy, 48% mineralization takes place in oxygen saturated solution whereas under aerated condition same was observed to be lowered to 38%.     

Determination of radiolysis products in gamma-irradiated multilayer barrier food packaging films containing a middle layer of recycled LDPE

Volatile and non-volatile radiolysis products and sensory changes of five-layer food packaging films have been determined after gamma irradiation (5–60 kGy). Barrier films were based on polyamide (PA) and low-density polyethylene (LDPE). Each film contained a middle buried layer of recycled LDPE or 100% virgin LDPE (control samples). Data showed that a large number of radiolysis products were produced such as hydrocarbons, alcohols, carbonyl compounds, carboxylic acid. These compounds were detected in the food simulant after contact with all films even at the lower absorbed doses of 5 and 10 kGy. The type and concentration of radiolysis products increased progressively with radiation dose, while no new compounds were detected as a result of the presence of recycled LDPE. In addition, irradiation dose appears to influence the sensory properties of table water in contact with films.     

Radiolysis of 1-naphthol in aqueous solutions

The effects of absorbed doses, initial pH and 1-naphthol concentration onto its radiolysis in aqueous sulphuric and hydrochloric acids by gamma rays from ⁶⁰Co were investigated. Under the experimental conditions, 1-naphthol degradation yields increased with increasing the absorbed doses (0.3–3.0 kGy) and with decreasing the initial 1-naphthol concentration (20–1 ppm). It was found out that the hydrated electrons did not play any significant roles in 1-naphthol radiolysis, as the degradation yields were higher at pH₀ ~ 0.46 compared to those at pH₀ ~ 2.0–5.0. The corresponding radiolytic yields G(−1-naphthol) were (6.13 ± 1.00)) × 10⁻² and (5.11 ± 0.22) × 10⁻² μmol/J in sulphuric acids, (15.61 ± 3.85) × 10⁻² and (4.76 ± 0.48) × 10⁻² μmol/J in hydrochloric acids. 1-Naphthol degradation rates could be described by the kinetic equations of pseudo-first-order reactions. An empirical relation between the observed reaction constants k _D and the initial 1-naphthol concentrations was established, enabling to predict the absorbed doses required for a given treatment efficiency. Three products of 1-naphthol degradation were revealed using an HPLC/UV procedure.     

High-energy ionising radiation initiated decomposition of acetovanillone

Hydroxyl radical, hydrated electron and hydrogen atom intermediates of water radiolysis react with acetovanillone with rate coefficients of (1.05±0.1)×10¹⁰, (3.5±0.5)×10⁹ and (1.7±0.2)×10¹⁰mol^?1 dm³ s^?1. Hydroxyl radical and hydrogen atom attach to the ring forming cyclohexadienyl type radicals. The hydroxyl–cyclohexadienyl radical formed in hydroxyl radical reaction in dissolved oxygen free solution partly transforms to phenoxyl radical. In the presence of O₂ phenoxyl radical formation and ring destruction are observed. Hydrated electron in O₂ free solution attaches to the carbonyl oxygen and undergoes protonation yielding benzyl type radical. In air saturated 0.5 mmol dm^?3 solution using 15 kGy dose most part of acetovanillone is degraded, for complete mineralisation five times higher dose is required. The experiments clearly show that acetovanillone can be efficiently removed from water by applying irradiation technology.     

Radiolysis of N,N-dimethylhydroxylamine and its radiolytic liquid organics

N,N-dimethylhydroxylamine (DMHA) is a novel salt-free reducing reagent used in the separation U from Pu and Np in the reprocessing of power spent fuel. This paper reports on the radiolysis of aqueous DMHA solution and its radiolytic liquid organics. Results show that the main organics in irradiated DMHA solution are N-methyl hydroxylamine, formaldehyde and formic acid. The analysis of DMHA and N-methyl hydroxylamine were performed by gas chromatography, and that of formaldehyde was performed by ultraviolet–visible spectrophotometry. The analysis of formic acid was performed by ion chromatography. For 0.1–0.5 mol L⁻¹ DMHA irradiated to 5–25 kGy, the residual DMHA concentration is (0.07–0.47) mol L⁻¹, the degradation rate of DMHA at 25 kGy is 10.1–30.1%. The concentrations of N-methylhydroxylamine, formaldehyde and formic acid are (8.25–19.36) × 10⁻³, (4.20–36.36) × 10⁻³ and (1.35–10.9) × 10⁻⁴ mol L⁻¹, respectively. The residual DMHA concentration decreases with the increasing dose. The concentrations of N-methylhydroxylamine and formaldehyde increase with the dose and initial DMHA concentration, and that of formic acid increases with the dose, but the relationship between the concentration of formic acid and initial DMHA concentration is not obvious.     

Degradation of n-butylparaben and 4-tert-octylphenol in H2O2/UV system

The degradation of two endocrine disrupting compounds: n-butylparaben (BP) and 4-tert-octylphenol (OP) in the H₂O₂/UV system was studied. The effect of operating variables: initial hydrogen peroxide concentration, initial substrate concentration, pH of the reaction solution and photon fluency rate of radiation at 254 nm on reaction rate was investigated. The influence of hydroxyl radical scavengers, humic acid and nitrate anion on reaction course was also studied. A very weak scavenging effect during BP degradation was observed indicating reactions different from hydroxyl radical oxidation. The second-order rate constants of BP and OP with OH radicals were estimated to be 4.8×10⁹ and 4.2×10⁹ M^?1 s^?1, respectively. For BP the rate constant equal to 2.0×10¹⁰ M^?1 s^?1was also determined using water radiolysis as a source of hydroxyl radicals.     

Effect of gamma irradiation on molecular weight of fluorinated aromatic polyethers

A series of fluoropolymer films was synthesized by reacting 1,3-bis(1,1,1,3,3,3-hexafluoro-2-pentafluorophenylmethoxy-2-propyl)benzene (12F-FBE) with a series of bisphenol monomers via a polycondensation reaction. The biphenols used included a diphenol-substituted spirodilactam, biphenol, bisphenol A, bisphenol AF, bisphenol F and bisphenol O. Polymers films from these new fluoropolyaryl ethers were irradiated by a Gamma Beam 657-PT at a dose rate of 9 kGy/h; the absorbed dose was varied between 30 and 150 kGy. The effect on the chemical structure upon radiation was studied by DSC, TGA, FTIR-ATR, NMR, and GPC, both before and after irradiation. The data obtained allowed the determination of the degradation radiochemical yield (G _s), between 0.24 and 7.43 crosslinking radiochemical yield (G _x), from 0.03 to 1.47 and the ratio of G _s/G _x was between 2.89 and 8.28. There was no apparent physical change, from 30 to 150 kGy; the films continue to be flexible and transparent after irradiation.