الفهرس 
Title: Analytical Study of Some Human and Veterinary Drugs Used in the Treatment of GIT Disorders
ContentOnly 14 pages are availabe for public view
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Abstract
This thesis involved analytical study of some drugs used in the treatment of GIT disorders and described simultaneous analysis of binary or quaternary mixtures by applying spectrophotometric, chemometric-assisted spectrophotometric and chromatographic methods. The aim of work was to develop several simple, accurate, sensitive, selective and precise methods for the assay of the studied drugs (doxycycline hydrochloride, tylosin tartrate, sulphaquinoxaline sodium, sulphadimidine sodium, diaveridine and vitamin K3) in their pure powdered form, laboratory-prepared mixtures and veterinary formulation. An application involving analysis of residues of doxycycline hydrochloride and tylosin tartrate in chickens was adopted.
The first part presents simple introduction on GIT and its main disorders with a brief of the common agents used in their management. The second part provided a pharmaceutical background about the chemistry, mode of action and literature review of the reported analytical methods of doxycycline hydrochloride (DOX) and tylosin tartrate (TYT).
Different manipulating pathways were applied for simultaneous determination of mixtures of DOX and TYT in their pure powdered form and veterinary formulation using either successive or progressive resolution techniques without prior separation steps. Some of these methods were based on relationship of the values of the recorded responses at two selected wavelengths such as absorbance values at zero-order spectra, amplitude values of ratio spectra or derivative or amplitude of derivative of the ratio spectra. Thus, mathematic relevance was applied either as difference, difference coupled with factor or regression manipulation or factor only or summation in order to enhance the resolution power and evaluate the potency of each component in the medicine, separately.
The first pathways based on the absorbance of the scanned zero-order absorption spectra were namely, dual wavelength (DW), induced dual wavelength (IDW), absorption correction (AC), absorbance subtraction (AS) and advanced absorbance subtraction.
The second pathway based on the derivative of zero-order absorption spectra were first derivative (D1), amplitude correction and amplitude summation. The third pathway was based on the ratio spectra of the zero-order absorption spectra includes ratio difference (RD), ratio subtraction (RS) coupled with EXRS, CM and SS methods, amplitude modulation (AM), advanced amplitude modulation (AAM) and concentration value methods. The forth pathway was based on ratio spectra of the derivative spectra includes derivative subtraction (DS) coupled with CM and SS methods. Finally, the fifth pathway was based on derivative of ratio spectra is derivative ratio method (DD1).
The specificity of the developed methods was investigated by analyzing laboratory-prepared mixtures and veterinary formulation containing the studied drugs with no interference from additives. The proposed methods were validated according to ICH guidelines. The obtained results were statistically compared with those of the official methods; using Student’s t-test, F-test, showing no significant difference with respect to accuracy and precision.
RP-HPLC method was successfully applied for simultaneous determination of DOX and TYT in their pure powdered form, laboratory-prepared mixtures and veterinary formulation. The proposed method was validated as per ICH guidelines for linearity, range, accuracy, precision and specificity. The results were found to be within the acceptable limits.
RP-HPLC has been developed to quantitatively determine DOX and TYT residues in different chicken tissues (muscle, fat and liver). The studied chickens received a recommended dose of a binary mixture of the two drugs (Tydovet®). The study aimed to estimate the withdrawal time of both drugs in chicken tissues. The analysis was done by solvent extraction and solid-phase extraction for clean-up of samples from the tissue matrix, followed by liquid chromatographic determination of the cited drugs with UV-detection. Sixty specific pathogen free chickens (SPF) were used. The first group (50 chickens) administered the recommended dose of Tydovet®. A multiple-dose of (1 g/L of Tydovet powder) was administered by oral route every 24 h. for 5 successive days. The two other groups were positive and negative control groups, and each group consisted of 5 chickens which didn’t receive any treatment. Successive samples were taken daily and analyzed for residues of DOX and TYT. Residue decline with time was tracked to conclude the safe time to eat different tissues.
The third part provided a pharmaceutical background about the chemistry, mode of action and literature review of the reported analytical methods of sulphadimidine sodium (SDS), sulphaquinoxaline sodium (SQS), diaveridine (DVD) and vitamin K3 (VTK3).
Different resolutions were applied for simultaneous determination of SDS, SQS, DVD and VTK3 in pure powdered form and veterinary formulation without prior separation steps. These manipulations were applied such as successive ratio subtraction (SRS) coupled with constant multiplication (SRS-CM), absorbance subtraction (AS) and amplitude modulation method (AM). The specificity of the developed methods was investigated by analyzing laboratory-prepared mixtures and veterinary formulation containing the studied drugs with no interference from additives. The proposed methods were validated according to ICH guidelines. Green chemistry is a current topic that is globally encouraged by researchers with environmental awareness. It was applied to reduce the negative effects of chemical products on human health and the environment. The obtained results were statistically compared with those of the official or reported methods; using Student’s t-test and F-test, showing no significant difference with respect to high accuracy and precision.
Two chemometric-assisted spectrophotometric models, Principal Component Regression (PCR) and Partial Least Square (PLS) were developed for simultaneous determination of SDS, SQS, DVD and VTK3 in their pure powdered form and veterinary formulation. The first step in determination of the studied drugs by multivariate calibration models involved constructing the calibration matrix for the quaternary mixture. The calibration set was obtained by using the absorption spectra set of 15 mixtures of all cited drugs with different ratios of each component listed and measured at 223 - 268 nm. In this study, the leave one out crossing validation was used and the root mean square error of cross validation (RMSECV) values were used as diagnostic tests for examining the errors in the predicted concentrations. RMSECV values indicated both precision and accuracy of predictions. The proposed models were applied to predict the concentrations of SDS, SQS, DVD and VTK3 in the validation set of 9 mixtures to validate the prediction ability of the suggested models. The two models were applied for the analysis of all drugs in veterinary formulation. The proposed models were validated according to ICH guidelines. The obtained results were statistically compared with those of the official or reported methods; using Student’s t-test and F-test, showing no significant difference with respect to high accuracy and precision. The developed models are time saving, economic and environmentally-friendly since no chemical reagents or harmful organic solvents were used.
RP-HPLC method with UV detection was established for simultaneous determination of a veterinary quaternary mixture of SDS, SQS, DVD and VTK3 in pure powdered form, laboratory-prepared mixtures and veterinary formulation.
The proposed method was validated according to ICH guidelines. The obtained results were statistically compared with those of the official or reported methods; using Student’s t-test and F-test, showing no significant difference with respect to high accuracy and precision. A simple and proficient approach for profiling the greenness of HPLC method was presented. This environmental assessment tool (EAT) takes into consideration the environmental, health and safety issues for all solvents that involved in the chromatographic method and calculates a total score that can be used for comparison of the greenness of different methods.
The forth part provided statistical comparison of the results was obtained by applying one-way ANOVA for the purpose of comparison of the developed methods with those of the official and reported methods, which showed that there was no significant difference between them for the determination of DOX and TYT regarding accuracy and precision. One-way ANOVA was applied for the purpose of comparison of the developed methods with those of the official and reported methods, which showed that there was no significant difference between them for the determination of SDS, SQS, DVD and VTK3 regarding accuracy and precision.