The evaluation of the potential to use Ultra Performance Liquid Chromatography (UPLC) for the simultaneous quantification of all the actives in a multi-active tablet is described in this work. Part of the evaluation was to ensure that the necessary regulatory requirements were adhered to by ascertaining that an analytical method is suitable for a specific purpose through analytical method validation for the specific multi-active tablet. The UPLC method was also tested for the analysis of similar products, namely tablet formulations that contain similar active ingredients in the same proportions but with an additional active ingredient. A method for the simultaneous determination of paracetamol, caffeine and codeine phosphate was developed using UPLC technology. The UPLC developed method was more efficient than the existing in-house HPLC method. The UPLC method was then validated in accordance to ICH and USP guidelines. The application of this UPLC method for the analysis of similar products containing paracetamol, caffeine, codeine phosphate and one extra active ingredient was very challenging. The low concentration of the additional component, differences in sample matrix and differences in formulations added to the challenges. The direct application for the analysis of products Y and Z was not successful; however the method could be used as a platform for further research. A cost comparison between the UPLC and HPLC methods showed the UPLC method to be more cost effective. Thus, while maintenance costs are higher for the UPLC instrument, column costs are comparable to HPLC columns, but solvent and waste disposal charges decrease considerably due to lower solvent use. The reduction in instrument time dramatically improves the cost effectiveness of UPLC over HPLC due to a concurrent reduction in analyst time requirement. The results of this study show that the analytical costs associated with the analysis of multi-active drugs using HPLC procedures can be reduced substantially by the CONFIDENTIAL INTELLECTUAL PROPERTY OF ASPEN PHARMACARE implementation of UPLC technology. The hypothesis that the enhanced chromatographic power of UPLC can be leveraged to provide faster analysis times hence increased product throughput rates, and lower operating costs for the analysis of multi-active drugs was accepted. These advantages were achieved whilst meeting all regulatory requirements for analytical methods as required by regulatory bodies.

The objective of this investigation was to develop quantitative isocratic HPLC methods for the analysis of digoxin and digitoxin. An HPLC system that employs a reverse-phase column, UV detection at 220 nm and solvent systems consisting of various proportions of water, methanol, isopropanol and dichlormethane was developed for the separation of digoxin, digitoxin and their potential degradation products and metabolites. HPLC separations of the above compounds by isocratic, solvent switchover and gradient elution modes were carried out in chromatographic times of 27, 16 and 13 minutes, respectively. For purposes of monitoring the separation of dihydro metabolites of digoxin, a 100% fluid recovery system was developed for use in the HPLC analysis of digoxin and its metabolites after fluorogenic post-column derivatization using the air-segmentation process. As an evidence of selectivity, the isocratic HPLC systems were utilized for the separation of a mixture of ten closely related steroids and the isolation of digitoxin from Digitalis purpurea leaf. The isocratic HPLC systems were found to be applicable for the quantitative analysis of digoxin and digitoxin in their respective dosage forms. The HPLC assay of digoxin and digitoxin dosage forms was carried out in less than forty-five minutes. These methods were found to be precise, accurate, sensitive enough for single tablet assay, and capable of simultaneously monitoring the potential degradation products or metabolites of digoxin and digitoxin. A comparison of the assay of digoxin and digitoxin dosage forms by HPLC and USP methods indicated that: (a) the precision and accuracy of both methods were comparable and within acceptable limits; (2) analysis by HPLC can be completed in less than forty-five minutes whereas the USP methods require over four hours; and (3) the HPLC methods have the advantages of higher sensitivity, selectivity and simplicity over the USP methods. The HPLC methods were used for the stability study of digoxin and digitoxin in their respective dosage forms. Lanoxin and digitoxin tablets were found to be stable under all the conditions of storage used in this study. Natigoxin tablets, Lanoxin injection and elixir were found to be subject to varying degrees and patterns of degradation. On the basis of the stability results it was observed that the assortment of pathways that may be involved at different conditions and times of storage'would make it difficult to estimate digoxin shelf-life from data obtained by accelerated aging. From the results of this investigation, it was concluded that the isocratic HPLC methods were suitable for the assay of digoxin and digitoxin dosage forms as well as for purposes of stability testing and simultaneous monitoring of degradation products or metabolites. This abstract represents the true contents of the thesis submitted. / Pharmaceutical Sciences, Faculty of / Graduate

No description available.

Thesis (Ph. D.)--Florida State University, 2004. / Advisor: Dr. John G. Dorsey, Florida State University, College of Arts and Sciences, Dept. of Chemistry and Biochemistry. Title and description from dissertation home page (viewed Jan. 19, 2005). Includes bibliographical references.

Thesis (Ph. D.)--Brigham Young University. Dept. of Chemistry and Biochemistry, 2004. / Includes bibliographical references.

No description available.

Typescript (photocopy). / Digitized by Kansas Correctional Industries

No description available.

During the course of study of reversed phase ion partition chromatography, it was observed that non-ionic substances such as alcohols, ester, and ketones undergo chromatographic separation in some as yet undefined association with cationic dyes (methylene blue chloride or brilliant green). Detection of non-chromophore trace level compounds has been a major problem in liquid chromatography due to the lack of a universal detector. Refractive index detector, although a universal detector lacks sensitivity. The U.V. absorbance detector is the work horse of liquid chromatography. Its major drawback is its lack of universality. It is often desirable to extend the utility of this detector to compounds toward which they are normally insensitive. This research was directed to developing the U.V.-Visible absorbance detector into a 'universal detector'. Using a mixture of methanol/water or dioxane/water solvent containing 1 x 10⁻⁴ M cationic dye such as the mobile phase it was shown to separate on Partisil ODS or on Zorbax ODS a series of C₂-C₅ alcohols and other neutrals at submicrogram levels with good base line separation. The alcohols carry with them some dye which must come from the presaturated dye ODS column. The dye peaks are detected spectrophotometrically at λ maximum of dye and becomes a measure of the eluting alcohol concentration. Normally, these aliphatic alcohols have a poor sensitivity either with refractive index or U.V. absorbance detector. This novel mode of detection and separation of trace quantities of alcohols and other neutral species represents a significant increase in sensitivity and should be widely applicable. The experimental data on which these separations are based, poses very interesting questions. For example, is there a specific kind of interaction between the alcohol and the dye or do the alcohols distribute between the Partisil ODS and mobile phase in their customary fashion and dissolve some of the immobilized dye because of their local excess concentration? Furthermore why do the slopes of the linear calibration curves obtained for each of the alcohols vary with the particular alcohol? Retention model based on dye alcohol complex formation and equilibrium partitioning of these species is advanced.

Significant advances in the understanding of chemical interactions at the solid-liquid interface have been made in this research through the use of diagnostic separations as a surface analysis technique. Diagnostic liquid chromatography has been employed in a detailed investigation of the thermodynamic and kinetic quantities which describe the interactions associated with a temperature induced conformational change in the octadecyldimethylsilane moieties of two different bonded silica materials. As a result of this study the nature of the structure and interactions of the ∼20Å thick interfacial region which acts as the stationary phase in reversed-phase liquid chromatography (RPLC) has been elucidated. The location and orientation of the average intermolecular interactions in the solvated layer stationary phase for solutes of differing hydrogen bonding ability and geometry has been determined as affected by bonded surface coverage, solvent hydrogen bonding competition and the structure of the solvated layer. These refinements in the model of the stationary phase solvated layer provide a much more detailed and accurate description of the intermolecular interactions responsible for retention and selectivity in RPLC than was previously available. A new modification of the method of measuring column mobile phase volume in RPLC employing retention linearization of an homologous series of compounds has been described from fundamental themodynamic principles and a statistically valid data reduction approach. The added advantage of providing thermodynamic information about the chromatographic system under study is inherent in this new technique. The experimental and theoretical bases for the new separation technique of magnetic field-flow fractionation (magnetic FFF) have been demonstrated. It has been shown that FFF techniques can be used in a diagnostic mode to study the dynamic stability of particle suspensions. The application of an external magnetic field to non-aqueous suspensions of sub-micron sized γFe₂O₃ particles, whose surface character has been modified by the adsorption of water, has been shown to enhance the suspension stability with respect to sedimentation. With the choice of proper operational conditions, magnetic FFF has also been demonstrated to be useful in monitoring particle flocculation as a result of its ability to separate particle flocculates on the basis of size.