Menbutone is often used to stimulate the hepato-digestive activity in case of digestive disorders and hepatic insufficiency in different species (cattle, sheep, goats, pigs, horses, dogs) because it has choleretic and cholagogue effects and increases gastric and pancreatic juices. The objective was to develop and validate an HPLC method to quantify menbutone in sheep plasma using sparfloxacin as internal standard. The HPLC mobile phase consisted of acetonitrile:monopotassium phosphate solution. The method was validated according to EMA guideline (EMEA/CHMP/EWP/192217/2009). Mean retention times of menbutone and sparfloxacin were 4.5 and 2.2 min, respectively. The method met all specifications of the EMA guideline, being selective and linear in the range of 0.2–100 µg/mL (R2 ≥ 0.99). The within-run precision range was 0.19–8.21%, with an accuracy of 102.99–119.52% for the lower limit of quantitation (LLOQ). For the other values (LOW, MED, HIGH) the precision range was 0.01–4.77%, with an accuracy of 85.17–109.67%. The LLOQ was 0.2 µg/mL, and no interference from the biological matrix was found. Stability of menbutone in the biological matrix at different storage conditions was also demonstrated. Thus, the method can be used to determine menbutone concentrations in plasma sheep in different types of studies.
In distributed agent architecture, tasks are performed on multiple computers which are sometimes spread across different locations. While it is important to collect security critical sensory information from the agent society, it is equally important to analyze and report such security events in a precise and useful manner. Data mining techniques are found to be very efficient in the generation of security event profiles. This paper describes the implementation of such a security alert mining tool which generates profiles of security events collected from a large agent society. In particular, our previous work addressed the development of a security console to collect and display alert message (IDMEF) from a Cougaar (agent) society. These messages are then logged in an XML database for further off-line analysis. In our current work, stream mining algorithms are applied for sequencing and generating frequently occurring episodes, and then finding association rules among frequent candidate episodes. This alert miner could profile most prevalent patterns as indications of frequent attacks in a large agent society.
The pharmacokinetic interaction between a benzimidazole (albendazole, ABZ) and a choleretic drug (menbutone, MEN) was evaluated in sheep. The plasma disposition of albendazole sulfoxide (ABZSO, active metabolite) and albendazole sulfone (ABZSO2, inactive metabolite) was investigated following an oral administration of albendazole (ABZ) (5 mg/kg) alone or with menbutone (MEN) (intramuscular, 10 mg/kg). Blood samples were collected over 3 days post-treatment, and drug plasma concentrations were measured by high performance liquid chromatography (HPLC). ABZSO was measured from 0.5 to 48 h, and ABZSO2 from 2 to 60 h. No parent drug was detected at any sampling time. Mean maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were 12.8% and 21.5% higher for ABZSO when ABZ and MEN were administered together, which indicates a significant increase in the amount absorbed. The rate of absorption was not modified, with similar values for the time to reach Cmax (tmax) (11.5 h with ABZ + MEN and 10.7 h with ABZ treatment), although no significant differences were observed for these latter pharmacokinetic parameters. Regarding ABZSO2, Cmax, AUC and tmax values were similar after both treatments (ABZ or ABZ + MEN). The results obtained indicate that co-administration of ABZ and MEN may be an interesting and practical option to increase the efficacy of this anthelmintic.
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