Pharmacokinetics of spinosad and milbemycin oxime administered in combination and separately per os to dogs.

Pharmacokinetic (PK) studies were conducted to determine the potential PK interactions when spinosad and milbemycin oxime (MBO) are administered simultaneously. Investigations used commercial MBO tablets (C-MBO; Interceptor(®) Flavor Tabs, active ingredient MBO, Novartis Animal Health, Greensboro, NC, USA), novel-source (Elanco) MBO (E-MBO) in a gelatin capsule, spinosad API (Active Pharmaceutical Ingredient using registered manufacturing process) in a gelatin capsule, spinosad tablets (Comfortis(®) chewable beef flavored tablets, active ingredient spinosad, Elanco Animal Health, Greenfield, IN, USA), and the recently registered spinosad + E-MBO combination tablets (Trifexis™ chewable beef flavored tablets, active ingredients E-MBO and spinosad, Elanco Animal Health, Greenfield, IN, USA). Regardless of the source of MBO, in the presence of spinosad, greater systemic exposure of MBO was obtained as compared to MBO administered alone. Target animal safety studies conducted with dose multiples of spinosad and MBO indicate the increased exposure of MBO does not have implications on adverse clinical reactions. Further research is required to determine whether the higher levels of MBO have any implications for improved effectiveness as compared to C-MBO. Effectiveness studies conducted with 0.5 mg/kg of E-MBO in combination tablets demonstrated noninterference against C-MBO with both products achieving >99% effectiveness against the dose-limiting nematode, Ancylostoma caninum. No statistical differences were detected in the PK of MBO when comparing animals receiving E-MBO (without spinosad) and C-MBO. Also, the PK of spinosad was unaltered when co-administered with MBO.

Electrocatalysis at a conducting composite electrode doped with a ruthenium(II) metallodendrimer.

A pentaerythritol-based metallodendrimer with RuIIterpyridine units was synthesized and tested as a mediator for the electrochemical oxidation of methionine (L-Met), cystine (L-Cys), and AsIII. A reversible oxidation of RuII was observed with the metallodendrimer as a solute in mixed acetonitrile-water solvents and as a component of carbon-based conducting composite electrodes. Mediated oxidation of the test species was observed. In aqueous solution, the composite electrode yielded a cyclic voltammetric peak current for the oxidation of L-Met in a 0.1 M phosphate buffer (pH 7.0) at 1.1 V vs Ag/AgCl. This anodic process was employed for amperometric detection in a flow system. Linear calibration curves were obtained over the range 1.0-10 microM Met and Cys. Using the criterion of the concentration yielding a signal 3 times the uncertainty of a blank, detection limits of 0.6 and 0.5 microM were calculated for Met and Cys, respectively. The slopes with three nominally identical electrodes varied by 10%.

Donnan dialysis preconcentration coupled with ion chromatography and electrocatalytic oxidation for the determination of cyanide.

An electrocatalytic amperometric detector for the ion chromatographic determination of CN(-) is described. A conducting composite that is based on a graphite-loaded sol-gel material comprises the working electrode. The composite is doped with a Ru(II) metallodendrimer which is demonstrated to promote the electrochemical oxidation of CN(-) at potentials positive of 0.5 V vs. Ag/AgCl. In 6 mM NaOH, 0.05 M NaCl flowed at 1.0 ml min(-1), a 5-point calibration curve with the following linear least squares parameters is obtained over the range, 1.0-30 M CN(-): slope, 24.2+/-0.1 nA M(-1); intercept, -6+/-2 nA; and r, 0.9997. The detection limit, 0.7 muM CN(-), compares favorably to that obtained by amperometry at a silver electrode, 0.5 muM CN(-), under comparable experimental conditions. A 60-min preconcentration by Donnan dialysis increases the sensitivity by a factor of 23.6.

Oxidation at a sol-gel composite electrode doped with a dirhodium-substituted polyoxometalate for amperometric detection of peptides separated by HPLC.

Oxidation of a variety of compounds, including methionine (Met), using a complex formed between dirhodium(II) acetate and the lacunary form of phosphotungstic acid as the catalyst is effective over a wide range of conditions, including pH 2-10. Thus, amperometric detection at a composite in which this complex is immobilized in a sol-gel material does not place restrictions on selection of conditions for separations by reverse-phase HPLC. A demonstration of this point is shown by a study of Met, Met-Phe, Phe-Met, Met-Met, and Gly-Met-Gly (Phe, phenylalanine; Gly, glycine). Using a 0.05 M phosphate buffer at pH 6.7, a C18 column, and a flow rate of 1 ml min(-1), capacity factors for Met, Gly-Met-Gly, Met-Met, and Phe-Met were 1.4, 2.1, 5.6, and 34, respectively. Phe-Met and Met-Phe co-eluted.