Ion fragmentations via photoelectron activated radical relays and competed hole oxidization on semiconductor nanoparticles for mass spectrometry.

Structural identification is challenging in mass spectrometric imaging because of inadequate sample quantities and limited sampling time in each pixel for tandem mass spectrometry (MS/MS) experiments, which are usually used for the generation of fragment ions. We report herein the observation of a cascade of highly specific chemical bond cleavages via a low-energy photoelectron activated radical relays and a competed hole oxidization on surfaces of (Bi2O3)0.07(CoO)0.03(ZnO)0.9 semiconductor nanoparticles irradiated with the 3rd harmonic (355 nm) of the Nd3+: YAG laser. Distinguished from high energy electron impact (EI), this approach generates gaseous radical anions through the exothermic capture of low-energy tunneling electrons that are not able to cause extensive vibrational excitations. It was found not only original radical center but also secondary or even tertiary radical centers cause specific bond cleavages exclusively on α positions. The original radical center directly activates the cleavages of α-positioned chemical bonds that cause the formation of secondary radical centers. Ion fragmentations proceed along the newly formed radical centers that further activate the cleavages of their α-positioned chemical bonds. Using 8 compounds, we have demonstrated various radical reactions involved in desulfonation, cyclization, and ring contraction reactions as well as competed hole oxidization-generated hydroxyl radical substitution reactions. The interpretable fragment ions provide unambiguous experimental evidences for structural elucidation of drug residues and metabolites in mass spectrometric imaging of tissue slices without tandem mass spectrometry (MS/MS).

Structural elucidation of sulfaquinoxaline metabolism products and their occurrence in biological samples using high-resolution Orbitrap mass spectrometry.

Four previously unreported metabolism products of sulfaquinoxaline (SQX), a widely used veterinary medicine, were isolated and analyzed using liquid chromatography coupled to high-resolution Orbitrap mass spectrometry. Metabolites were structurally elucidated, and a fragmentation pathway was proposed. The combination of high-resolution MS(2) spectra, linear ion trap MS(2), in-source collision-induced dissociation (CID) fragmentation, and photolysis were used to analyze SQX and its metabolites. All metabolism products identified showed a similar fragmentation pattern to that of the original drug. Differential product ions were produced at m/z 162 and 253 which contain the radical moiety with more 16 Da units than sulfaquinoxaline. This occurs by a hydroxyl attachment to the quinoxaline moiety. With the exception of two low-intensity compounds, all the mass errors were below 5.0 ppm. The distribution of these metabolites in some animal species are also presented and discussed.

Stability of sulfaquinoxaline, sulfadimethoxine, and their N4-acetyl derivatives in chicken tissues during frozen storage.

The N4-acetyl derivatives of sulfaquinoxaline and sulfadimethoxine were stable in fortified chicken liver and thigh muscle tissues during frozen storage for 1 year at -20 and -70 degrees C. In contrast, the parent compounds depleted approximately 35% in liver tissues at -20 degrees C. The transformation of the depleted sulfa drugs to their N4-glucopyranosyl derivatives was negligible, suggesting that products other than glucosides resulted during the storage period.

Liquid chromatographic analysis of sulfaquinoxaline and its application to pharmacokinetic studies in rabbits.

A specific, sensitive high-performance liquid chromatographic method is described for sulfaquinoxaline (I) and its major metabolite, the N4-acetyl metabolite (II), in biological fluids. Detection limits for I and II were 0.25 and 0.50 micrograms/mL in plasma and 0.10 and 0.20 micrograms/mL in urine, respectively. The pharmacokinetics of sulfaquinoxaline and its metabolite were studied in New Zealand White rabbits after individual doses of 50 mg/kg of sulfaquinoxaline and its metabolite were administered intravenously. Mean (+/- SD) plasma half-lives were 12.7 (8.0) h for sulfaquinoxaline and 15.4 (3.5) h for the metabolite. After administration of the N-acetyl metabolite sulfaquinoxaline appeared in the plasma and urine indicating that deacetylation had occurred. The repercussions of this observation are briefly discussed with respect to two rabbits in which plasma analyses and complete urine collections were made. As sulfaquinoxaline is administered prophylactically to rabbits by some breeders, it is recommended that investigators allow a washout period of about one week after receipt of the animals.

Some pharmacokinetic aspects of four sulphonamides and trimethoprim, and their therapeutic efficacy in experimental Escherichia coli infection in poultry.

Pharmacokinetic studies in broilers and layers of different sulphonamides indicate a good absorption and a long elimination half-life (of sulphaquinoxaline, sulphadimidine and to a lesser degree sulphadiazine) resulting in high plasma concentrations during drinking water medication in the recommended therapeutic doses. In contrast drinking water medication with high concentrations of trimethoprim (up to 1,320 mg/liter) resulted in a maximal mean plasma concentration of 1.2 micrograms/ml. Very good therapeutic effects were demonstrated in broilers experimentally infected with a sulphonamide-susceptible E. coli strain when treated with sulphaquinoxaline (200 mg/liter), sulphadimidine sodium (2 gram/liter), sulphachloropyridazine 30 per cent (1 gram/liter) and to a lesser degree sulphadiazine sodium (250 mg/liter). Synergism was demonstrated between trimethoprim and sulphadiazine (1:5). The combination of trimethoprim with sulphaquinoxaline (1:3) did not induce better therapeutic effects than sulphaquinoxaline in proportional doses. However, significant synergism was demonstrated between trimethoprim and both sulphonamides in treatment of experimental infection with sulphonamide-resistant E. coli. No signs resembling sulphonamide intoxication were observed during these studies.

Trace analysis of sulfaquinoxaline in animal tissues by high-performance liquid chromatography.

Sulfaquinoxaline (in combination with diaveridine as a potentiating agent) was administered orally to broilers, 4-5 weeks old, and sulfonamide residues were determined in muscle and liver at 0, 1, 2, 4, 6, 7, 8, and 10 days post-treatment, using ion-pair extraction followed by high-performance liquid chromatography with UV detection. Improved recoveries (ca. 80%, at the 10 ppb level) were obtained after liquefaction of the tissues by the addition of 8 M urea and sodium hydroxide, prior to ion-pair extraction. A withdrawal period of seven days was found necessary in order to reduce drug residues in muscle and liver to 10 ppb, a level without hazard to humans.