Veterinary Pharmaceutical Formulations Research Articles

Simultaneous Determination of Levamisole and Triclabendazole by Multivariate Calibration Models using Second Derivative Spectrophotometry in Veterinary Pharmaceutical Formulation

Simultaneous Determination of Levamisole and Triclabendazole by Multivariate Calibration Models using Second Derivative Spectrophotometry in Veterinary Pharmaceutical Formulation

Determination of Spiramycin and Oxytetracycline in binary mixtures by novel spectrophotometric methods with and without regression equation

Spiramycin (SPI) and oxytetracycline (OTC) are widely used antibacterial drugs. Thus, a great attention has been focusing on the development of a simple and selective analytical procedure for fast analysis of these compounds in a binary pharmaceutical mixture. Herein, we report four simple and reproducible spectrophotometric methods for determination of SPI and OTC in a binary mixture and in veterinary pharmaceutical formulations. A ratio difference (RD) based on the difference in the amplitude of the ratio spectra and dual wavelength methods were proposed for sensitive and selective determination of SPI in presence of OTC. Furthermore, Constant Value and Concentration Value based spectrophotometric methods were suggested for simultaneous determination of SPI and OTC in a binary mixture. The methods were successfully applied for the determination of SPI and OTC over the concentration range from 4.0 to 36.0 µg mL-1 and from 2.0 to 32.0 µg mL-1, respectively. The proposed methods were validated according to the International Conference on Harmonization (ICH) guidelines. The methods are accurate (100±1%), precise (%RSD ≤1.5) and cost-effective for determination of SPI and OTC in binary mixtures.

Voltammetric Determination of Sulfaclozine Sodium at Sephadex-modified Carbon Paste Electrode

The electrochemical behavior of Sulfaclozine Sodium (SLC) was studied at a bare and sephadex-modified carbon paste electrodes by cyclic voltammetry and square wave voltammetry. The cyclic voltammetry (CV) showed a well-defined irreversible oxidation peak at 0.94 V in Britton- Robinson buffer pH 7.0. The strong affinity of SLC to sephadex allowed accumulation of SLC at the surface of electrode and thus higher electrochemical sensitivity to SLC. The influence of sephadex loading, the pH of the solution and the scan rate on the peak current was studied. A linear calibration curve covering the concentration range from 0.005 to 1 mM was obtained using SWV. The method was successfully applied for the determination of SLC in the veterinary pharmaceutical formulations with satisfactory accuracy and precision.

Densitometric and Ratio Spectra Methods for Simultaneous Determination of Sulfaquinoxaline Sodium and Pyrimethamine in Binary Mixture

Four methods were developed for simultaneous determination of sulfaquinoxaline-Na and pyrimethamine in their combined pharmaceutical formulations. The first one was a densitometric method where chloroform-methanol (9: 1, v/v) was the developing system and the plates were scanned at 254 nm. The obtained spots appeared at Rf 0.64 and 0.35 and determined in the range of 0.5-10.0 μg/spot and 0.1-10.0 μg/spot for sulfaquinoxaline-Na and pyrimethamine, respectively. Furthermore, three spectrophotometric methods manipulating ratio spectra namely, ratio difference method, extended ratio subtraction method coupled with ratio subtraction method and mean centering method were established for the determination of the two studied drugs in the presence of propylene glycol as a solvent. Linear correlation was found over the concentration range of 2-25 μg mL-1 and 3-15 μg mL-1 for the two drugs, respectively. The proposed methods were successfully applied for analyzing the cited drugs in their veterinary pharmaceutical formulations. The obtained results were statistically analyzed and found to be in accordance with those given by a reported method. The validity of the methods was evaluated according to ICH guidelines.

Gold nanoparticles coupled with graphene quantum dots in organized medium to quantify aminoglycoside anti-biotics in yellow fever vaccine after solid phase extraction using a selective imprinted polymer

The determination of kanamycin sulfate was made indirectly by measuring its effect on photoluminescent amino functionalized graphene quantum dots (GQDs-amino) associated with gold nanoparticles (AuNPs) that were produced by the reduction of AuCl4 with NaBH4 in an aqueous dispersion of GQDs-amino (obtained by the pyrolysis of citric acid and glutathione) also containing the cationic surfactant CTAB. The AuNPs-GQDs-amino-CTAB system presents a suppressed photoluminescence that is amplified in the presence of kanamycin. Under optimized experimental conditions, the photoluminescence amplification of the nanomaterial system showed a linear response as a function of kanamycin concentration, covering three orders of magnitude (10−7 to 10−5 mol L−1). The use of solid phase extraction with a cartridge packed with aminoglycoside selective molecularly imprinted polymer ensured selectivity in determinations made on yellow-fever vaccine and veterinary pharmaceutical formulations. The analytical results were statistically similar to those obtained with an HPLC-based fluorescence method (after chemical derivatization). The proposed method is a simple, sensitive and selective approach that does not involve the use of toxic reagents employed for chemical derivatization of aminoglycoside antibiotics.

A Simple and Rapid HPLC Method for the Multidetermination of Enrofloxacin, Ciprofloxacin, and Oxytetracyclin in Raw Materials and Veterinary Pharmaceutical Formulations

A Simple and Rapid HPLC Method for the Multidetermination of Enrofloxacin, Ciprofloxacin, and Oxytetracyclin in Raw Materials and Veterinary Pharmaceutical Formulations

Evaluation of physicochemical properties as supporting information on quality control of raw materials and veterinary pharmaceutical formulations

This study aimed to show that the physicochemical proprieties obtained by Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TG), and scanning electronic microscopy (SEM) can be useful tools for evaluating the quality of active pharmaceutical ingredients (APIs) and pharmaceutical products. In addition, a simple, sensitive, and efficient method employing HPLC-DAD was developed for simultaneous determination of lidocaine (LID), ciprofloxacin (CFX) and enrofloxacin (EFX) in raw materials and in veterinary pharmaceutical formulations. Compounds were separated using a Gemini C18 (250 mm × 4.6 mm, 5 µm) Phenomenex® column, at a temperature of 25 °C, with a mobile phase containing 10 mM of phosphoric acid (pH 3.29): acetonitrile (85.7:14.3, v/v) and a flow rate of 1.5 mL/min. Physicochemical characterization by TG, FTIR, and SEM of raw materials of LID, CFX, and EFX provided information useful for the evaluation, differentiation, and qualification of raw materials. Finally, the HPLC method was proved to be useful for evaluation of raw material and finished products, besides satisfying the need for an analytical method that allows simultaneous determination of EFX, CFX, and LID, which can also be extended to other matrices and applications.

Tissue depletion study of enrofloxacin and its metabolite ciprofloxacin in broiler chickens after oral administration of a new veterinary pharmaceutical formulation containing enrofloxacin

• A new veterinary drug formulation containing enrofloxacina was studied in broiler chickens.

FOURIER TRANSFORM INFRARED SPECTROSCOPY, THERMOGRAVIMETRIC ANALYSIS, SCANNING ELECTRON MICROSCOPY AS SUPPORTING TOOLS IN QUALITY CONTROL OF ANTIPARASITICS

This study shows that Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and scanning electron microscopy (SEM) can be used as supporting tools for the evaluation of the quality of antiparasitics. In addition, an analytical methodology was developed and validated to quantify simultaneously thiabendazole (TB), febantel (FB), toltrazuril (TZ), and fluazuron (FZ) in bulk and in their veterinary pharmaceutical formulations using reverse phase high performance liquid chromatography (RP-HPLC). In order to investigate stability, pharmaceuticals were submitted to degradation processes under different conditions, such as recommended by the International Conference on Harmonization. The chromatographic conditions were optimized and the validation parameters, such as selectivity, linearity, detection limit, quantification limit, precision, accuracy, and robustness showed results within acceptable standards. All analytes were stable in the stability assays in acid and basic media and thermal conditions, except in the oxidation process, which presented two degradation peaks. Physicochemical characterization by TGA, FTIR, and SEM of raw materials of TB, FB, TZ, and FZ provided information about the authenticity of the analytes, proving the wide applicability of the instrumental techniques. The RP-HPLC proposed method was found to be accurate, precise, and reproducible and can in addition be used for routine quality control analysis.

Spectrophotometric Methods for Simultaneous Determination of Oxytetracycline HCl and Flunixin Meglumine in Their Veterinary Pharmaceutical Formulation.

Four precise, accurate, selective, and sensitive UV-spectrophotometric methods were developed and validated for the simultaneous determination of a binary mixture of Oxytetracycline HCl (OXY) and Flunixin Meglumine (FLU). The first method, dual wavelength (DW), depends on measuring the difference in absorbance (ΔA 273.4–327 nm) for the determination of OXY where FLU is zero while FLU is determined at ΔA 251.7–275.7 nm. The second method, first-derivative spectrophotometric method (1D), depends on measuring the peak amplitude of the first derivative selectively at 377 and 266.7 nm for the determination of OXY and FLU, respectively. The third method, ratio difference method, depends on the difference in amplitudes of the ratio spectra at ΔP 286.5–324.8 nm and ΔP 249.6–286.3 nm for the determination of OXY and FLU, respectively. The fourth method, first derivative of ratio spectra method (1DD), depends on measuring the amplitude peak to peak of the first derivative of ratio spectra at 296.7 to 369 nm and 259.1 to 304.7 nm for the determination of OXY and FLU, respectively. Different factors affecting the applied spectrophotometric methods were studied. The proposed methods were validated according to ICH guidelines. Satisfactory results were obtained for determination of both drugs in laboratory prepared mixture and pharmaceutical dosage form. The developed methods are compared favourably with the official ones.

A Validated HPLC Method for the Determination of Tiludronate Disodium on a Novel Brominated Stationary Phase

An analytical method for analysis of Tiludronate; [4-chlorothiophenyl) methylene] bisphosphonate known as Tildren® is developed without pre or post derivatization on a newly introduced halogenated stationary phase namely pentabromobenzyl column (PBr column) for the first time. The optimum HPLC conditions used are: A mobile phase composed of acetonitrile: Water: triethylamine: Acetic acid (50: 50: 0.05: 0.05; v: v: v: v), at a flow rate 0.5 mL/min, at temperature 35°C. Two wavelengths were selected from the UV-spectrum namely 197 and 267 nm. The method is linear in the range of 0.06-0.6 mg/mL with square of the regression coefficient (r2) 0.9998 at 197 nm. The limit of quantification (LOQ) is 0.040 mg/mL and the limit of detection (LOD) is 0.013 mg/mL. The method is precise with %RSD 0.41-1.36 (intra-day) and %RSD 0.38-1.91 (inter-day). The method is found to be robust at temperature 35°C ± 3°C, wavelength 197 nm ± 1 nm, pH of the aqueous phase ± 0.03 and %ACN 50% ± 1%. At 267 nm, the method is linear in the range of 0.08-0.8 mg/mL with r2 0.9997, LOQ is 0.050 mg/mL and LOD is 0.016 mg/mL. The %RSD for intra-day precision ranges from 0.96-1.74, while for inter-day precision ranges from 1.09-2.32. The method is proved robust in temperature 35°C ± 3°C, wavelength 297 nm ± 3 nm, pH of the aqueous phase ± 0.03 and %ACN 50% ± 1%. The method is accurate with % recovery ranged from 98.82-99.42% with %RSD ranging from 0.210-1.023. This method is suitable for the assay of tiludronate in both bulk and in its veterinary pharmaceutical formulations.

Simultaneous Determination of Sulphadiazine Sodium and Trimethoprim in Medicated Fish Feed, Fish Tissues and in Their Veterinary Pharmaceutical Formulation by Thin-Layer Chromatography-Densitometry

A specific, precise, and accurate thin-layer chromatographic method for the simultaneous estimation of sulphadiazine sodium (SDZ) and trimethoprim (TMP) in medicated fish feed and in fish tissues was developed and validated. This method is based on simple liquid extraction technique and employing thin-layer chromatography (TLC) as a cleanup step. In order to optimize the extraction procedure from fish tissues, several mobile phase systems and extracting solvents were tried. The method employed TLC aluminum plates precoated with silica gel 60 F254 as the stationary phase and chloroform-toluene-ethanol-glacial acetic acid (4.5:4.5:1.0:1.0 by volume) mixture as the developing solvent. This system was found to give compact and dense spots for both sulphadiazine sodium (RF value of 0.48) and trimethoprim (RF value of 0.16) without interference from either medicated fish feed or fish tissues coextractives. Densitometric analysis of both drugs was carried out in the reflectance-absorbance mode at 270 nm for SDZ ...

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 2298–1733cm−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 0.69mg per 100mg 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.

CO-DETERMINATION OF TWO ANTIPARASITICS DRUGS BY DERIVATIVE SPECTROPHOTOMETRY AND ITS PHOTODEGRADATION STUDIES

This work proposes a method for the co-determination of praziquantel and fenbendazole in veterinary pharmaceutical formulations (VPF) by second-derivative spectrophotometry at 226.4 nm (Zero-crossing method) and 324.6 nm (Graphic method), respectively. The excipients commonly used in VPF do not interfere. To obtain the optimal determination conditions, studies of solvent and light effects, were performed. The results of the light effects show that the expose of both drugs to indirect light and darkness does not produce any chemical change, since their zero-order spectra remained unchanged during the experiment. However, the exposition to the direct light only affects the fenbendazole. The zero order spectrum of FBZ in EtOH-HCl, present two broad bands (200 to 240 nm and 260 to 330 nm), these signals disappear and appear others totally different, at 230 nm and other with two peaks (285 and 295 nm). The FT-IR spectrum shows characteristics signals of the FBZ structure as the amide-NH group (3336.3 cm-1), this signal disappear indicating the bond break of the amide group caused by the exposition to sunlight for a time. These spectral changes evidenced a structural transformation as a result of photochemical decomposition in acid medium.

Simultaneous Determination of Albendazole and Praziquantel by Second Derivative Spectrophotometry and Multivariated Calibration Methods in Veterinary Pharmaceutical Formulation

The simultaneous determination of albendazole (ABZ) and praziquantel (PZQ) was performed by different mathematical approaches: second derivative spectrophotometry (SDS), classical least squares, regression of partial least squares and principal components regression based on spectral data of drugs dissolved in methanol-hydrochloric acid solution. The detection limits for multivariate calibrations were determined by creating a surrogate variable signal. SDS presented the best analytical features. The recoveries of ABZ and PZQ from the synthetic samples were near to 100 +/- 5%. The methods were applied in veterinary pharmaceutical formulation whose mass ratio ABZ:PZQ is 10:1; the results obtained were according to nominal content.

Validation of a novel HPLC sorbent material for the determination of ten quinolones in human and veterinary pharmaceutical formulations

A novel sorbent material of ultrapure silica gel provided with novel State of the Art Bonding- and Endcapping Technology commercially available under the name PerfectSil Target (250 x 4 mm, ODS-3, 5 microm, by MZ-Analysentechnik, Germany) was used and validated for the sensitive HPLC determination of ten quinolone antibiotics: enoxacin, ofloxacin, norfloxacin, ciprofloxacin, danofloxacin (DAN), enrofloxacin (ENR), sarafloxacin, oxolinic acid (OXO), nalidixic acid (NAL), and flumequine. The analytical column validation was performed in terms of separation efficiency, precision, and peak asymmetry. The separation was achieved at ambient temperature using a mobile phase of TFA (0.1%)-CH3OH-CH3CN delivered under the optimum gradient program, at a flow rate of 1.2 mU/min. Photodiode array detection was used and eluant was monitored at 275 nm. For the quantitative determination caffeine (7.5 ng/microL) was used as internal standard. The achieved LODs were 0.03 ng/microL per 50 microL injected volume for OXO, 0.1 ng/microL for DAN, ENR, and NAL, and 0.2 ng/microL for the remaining six studied quinolones. The method was validated in terms of interday (n = 6) and intraday (n = 5) precision and accuracy. The proposed method was successfully applied to the analysis of pharmaceutical formulations destined either for human or for veterinary use.

Method for determining the average degree of substitution of o-vanillin derivatized porcine somatotropin

Electrospray mass spectral observation directly on a sample of a derivatized protein, such as porcine somatotropin (pST), affords a method for evaluating the degree of substitution of this protein. Derivatization of the lysine residues and the terminal amino residue here by formation of a Schiff base with a small aromatic aldehyde (in this case, o-vanillin) affords stabilization of the protein so that it may be used in a controlled release veterinary pharmaceutical formulation. This method permits direct observation of substitutions, optimization of manufacturing procedures for producing a commercial product, and permits quality evaluation of material.