| Summary: | 博士 === 國立中山大學 === 海洋生物科技暨資源學系研究所 === 104 === A rapid and efficient multiresidue method that involves using improved QuEChERS method and LC–ESI–MS/MS was developed to measure trace levels of sulfonamides in fish tissues. This proposed method was proven to be a powerful, highly sensitive, and environmentally friendly analytical tool that requires minimal sample preparation. The typical MS/MS fragmentation patterns of the [M+H]+ were 156 m/z, 108 m/z, and 92 m/z. Separation was performed on HC-C18 columns with a gradient elution by using methanol and 5 mM ammonium acetate aqueous solution (adjusted to pH 3.5 with formic acid). This method was validated and exhibited favorable performance as well as acceptable accuracy (80.2–93.5%), precision (3.82–8.71%), sensitivity (limits of detection (LODs) 0.43–1.22 μg kg-1 and limits of quantification (LOQs) 1.27–3.71 μg kg-1), and an acceptable matrix effect (-18.2–18.4%). This methodology has been successfully applied in analyzing various fish tissue from local markets.
The pharmacokinetics of sulfamonomethoxine (SMM) were estimated after single oral administration (100 mg/kg body weight) to the tilapia at 25.0 °C and drug concentration–time profiles for blood and tissues were described by the non–compartmental model. In the pharmacokinetics studies, the results indicated high levels of SMM appeared usually in the well perfused tissues, such as liver and bile, whereas low levels of SMM were generally found in the poorly perfused tissues, such as muscle. Acetylation of SMM in tilapia following oral administration was 45% and N4-acetyl sulfamonomethoxine (AC-SMM) was the major acetylated metabolite observed. T1/2 of AC-SMM (46.2 h) was longer than of SMM (21.7 h) in blood. Redistribution occurred in blood SMM from 96 h to 120 h and in blood AC-SMM from 48 h to 72 h. With regard to the drug excretion pathway, it was concluded that SMM and AC-SMM were excreted mainly by the biliary in the tilapia. Moreover, bile excretion may result in enterohepatic cycling and to some extent retard drug elimination.
In the PK–PD modeling of SMM study, the Cmax (9.6 mg kg-1) was above MIC value of Aeromonas salmonicida subsp. Salmonicida (3.12 mg kg-1), Vibrio anguillarum (3.12 mg kg -1) and Vibrio harveyi (6.25 mg kg -1). These results illustrated that SMM can inhibit the growth of certain aquatic bacterial pathogens.
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