Chemometric quality inspection control of pyrantel pamoate, febantel and praziquantel in veterinary tablets by mid infrared spectroscopy.

This paper describes the development and validation of a new multivariate calibration method based on diffuse reflectance mid infrared spectroscopy for direct and simultaneous determination of three veterinary pharmaceutical drugs, pyrantel pamoate, praziquantel and febantel, in commercial tablets. The best synergy interval partial least squares (siPLS) model was obtained by selecting three spectral regions, 3715-3150, 2865-2583, and 2298-1733 cm(-1), preprocessed by first derivative and Savitzky-Golay smoothing followed by mean centering. This model was built with five latent variables and provided root mean square errors of prediction (RMSEP) equal or lower than 0.69 mg per 100 mg of powder for the three analytes. The method was validated according the appropriate regulations through the estimate of figures of merit, such as trueness, precision, linearity, analytical sensitivity, bias and residual prediction deviation (RPD). Then, it was applied to three different veterinary pharmaceutical formulations found in the Brazilian market, in a situation of multi-product calibration, since the excipient composition of these commercial products, which was not known a priori, was modeled by an experimental design that scanned the likely content range of the possible constituents. The results were verified with high performance liquid chromatography with diode array detection (HPLC-DAD) and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and were in agreement with the predicted values at 95% confidence level. The developed method presented the advantages of being simple, rapid, solvent free, and about ten times faster than the HPLC ones.

Influence of Bi 58 Nowy (38% dimethoate) on pyrantel embonate concentration in the liver of rats.

The aim of the study was to determine the concentration of pyrantel residues in the liver of rats in different time points after oral administration of pyrantel embonate as well as combined administration of the Bi 58 Nowy preparation (38% of dimethoate) and pyrantel embonate. The experiment was conducted in two stages involving different doses of compounds and modes of exposure. At the first stage, the animals were administered pyrantel embonate with a stomach tube at a dose of 1000 mg/kg b.w. twice in a two-week interval, i.e. on day 14 and 28, and the Bi 58 Nowy preparation with drinking water at a dose of 15.48 mg/kg b.w. for 28 days. At the second stage, the rats received pyrantel embonate at a dose of 400 mg/kg b.w. with a stomach tube for 3 consecutive days, whereas the Bi 58 Nowy preparation was administered at a dose of 38.7 mg/kg b.w. also with a stomach tube for 5 consecutive days. In the rats doubly administered with pyrantel embonate, its residues were present until day 14, whereas when the drug was administered for 3 consecutive days they were present until day 7 of the experiment. The maximum concentration of pyrantel embonate was found in the liver after the 3rd hour, whereas a considerable decrease occurred between the 3rd and the 12th hour. The combined administration of pyrantel embonate and the Bi 58 Nowy preparation caused a significant decrease in the concentration of pyrantel residues in the liver 3 and 6 hours after exposure, as compared to the rats receiving the drug alone.

Residues of dimethoate in the liver and AchE activity in blood of rats after exposure to dimethoate, and dimethoate and pyrantel embonate.

The study was aimed at determining the dimethoate residues in the liver and acetylcholinesterase (AChE) activity in blood of rats exposed to dimethoate (individual intoxication), and dimethoate and pyrantel embonate (simultaneous intoxication). The experiment was carried out in two stages where various doses of preparations and exposure manners were used. In the first stage of the experiment, dimethoate (1/25 LD50) was administered to animals per os for 28 days, and pyrantel embonate (1/2 LD550) twice, i.e. on the day 14th and 28th. In the second stage, dimethoate was administered for 5 days (1/10 LD50), and pyrantel embonate (1/5 LD50) on day 3, 4 and 5 from the beginning of dimethoate intoxication. The short presence of the dimethoate residues in the liver of the animals examined was found until the 2nd day after 28-day intoxication (1/25 LD50) and until 14th day after 5-day intoxication (1/10 LD50), however, a distinct decrease in this insecticide residues in the liver of (analysed groups of) rats occurred between the 3rd hour and the 2nd day after exposure. Dimethoate in both applied doses significantly reduced AChE activity in blood. After application of the higher dose, the inhibition of AChE was more pronounced, and the return of its activity to physiological values lasted considerably longer. Co-administration of pyrantel embonate and dimethoate, slightly influenced changes of the parameters analysed, which have been dependent not only on a dose and manner of pyrantel application but also on time which lapsed from exposure.

Effects of pyrantel pamoate on adult and preadult Toxocara canis worms: an electron microscope and autoradiography study.

Adult as well as preadult Toxocara canis isolated from the intestine of a beagle were incubated for 2, 4, and 14 h in medium containing either different concentrations of pyrantel pamoate (23.6, 236, and 2360 micrograms/ml medium) or tritiated pyrantel pamoate (2.36 micrograms/ml medium). These incubations were performed to study the effects of pyrantel pamoate on the morphology of the parasitic nematodes and to obtain information concerning the mode of uptake, the distribution, and the total amount of pyrantel pamoate ingested by T. canis. The results of the ultrastructure studies indicate that the intestine, hypodermis, and muscle cells are the organs that are predominantly affected by the drug. Additionally, it turned out that the duration of the treatment, i.e., the incubation time, was more important in determining the efficacy of pyrantel pamoate against T. canis than was the concentration itself. Autoradiography studies revealed that the adult worms ingest the drug orally, whereas preadults absorb pyrantel pamoate mainly through the whole body surface. Finally, measurements of the total amount of pyrantel pamoate taken up by T. canis indicated that adult worms can limit or even reduce the ingestion of pyrantel for more than 4 h, but then ingest large amounts of the drug. Preadult worms, however, absorb the drug more or less continuously during the first 14 h through the cuticula, albeit in lower concentrations than the adults. The different experiments elucidate differences in the uptake of pyrantel pamoate as well as in the total amount of drug ingested or absorbed by adult or preadult worms, leading to the assumption that repeated treatment with lower concentrations will be more effective than high concentrations given only once.

High-performance liquid chromatographic determination of oxantel and pyrantel pamoate.

A method is described for the determination of oxantel and pyrantel pamoate in proprietary broad spectrum anthelmintic tablets. Quantitation is performed by using an octyl Spherisorb column with a mobile phase consisting of acetonitrile and water modified with butylamine. Carbaryl-(1-naphthyl methylcarbamate) is used as internal standard.