Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1992. / Vita. Abstract. Includes bibliographical references (leaves 99-103). Also available via the Internet.

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.

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Thesis (Ph. D.)--University of Hawaii at Manoa, 1994. / Includes bibliographical references (leaves 86-90). / Microfiche. / xiii, 90 leaves, bound 29 cm

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 6 uppsatser.

Thesis (M.S.)--Youngstown State University, 1998. / Includes bibliographical references.

The development of the monograph of a commonly used Chinese medicine, Lini Semen, for the Hong Kong Chinese Materia Medica Standards (HKCMMS) was recorded. HKCMMS is a set of reliable and internationally recognized standards of Chinese medicine. The monograph of Lini Semen was proposed, endorsed, and under editorial phase for the publication of the 9th volume of HKCMMS. In the proposed HKCMMS monograph of Lini Semen, besides regular content such as macroscopic and microscopic identification, and TLC identification, a HPLC fingerprint method and two assay methods were developed. All methods were well-established and validated. TLC identification: Lini Semen n-hexane extract is identified on a HPTLC Silica gel RP-18 plate, with α-linolenic acid and linoleic acid as the markers. The developing system consisted of acetone, acetic acid and dichloromethane in the ratio of 5:4:2. The spraying reagent was 5% sulphuric acid - ethanol solution and the plate was observed under 366 nm. HPLC fingerprint: Fingerprint of Lini Semen was conducted on a HPLC system with a C8 column. Mobile phase consisted of (A) water and (B) acetonitrile and isopropanol (9:1). Six characteristic peaks, including α-linolenic acid and linoleic acid were detected under 210 nm. Assay: α-Linolenic acid and linoleic acid were detected from Lini Semen n-hexane extract under the same HPLC condition of the fingerprint of Lini Semen. The proposed total content of α-linolenic acid and linoleic acid was not less than 0.56%. Secoisolariciresinol diglucoside (SDG) was detected from hydrolysed Lini Semen extract by HPLC system with a C18 column. Mobile phase consisted of (A) water and (B) acetonitrile. The detection wavelength was 280 nm. The proposed content of SDG was not less than 0.81%. Conclusion: It is the first time to propose a HPLC fingerprint and introduce SDG as a assay marker of Lini Semen in a regional standard monograph. The established methods for TLC identification, HPLC fingerprint, assay of the total content of α-linolenic acid and linoleic acid, as well as assay for SDG were validated with in-house and inter-laboratory comparison to prove that the methods are reliable.

Erythromycin is a macrolide antibiotic used mainly in the treatment of infections caused by gram-positive organisms. Erythromycin base is rap idly degraded in acidic media necessitating the use of structurally modified erythromycin derivatives or acid resistant dosage forms in order to decrease gastric inactivation of the drug. The majority of pharmacokinetic studies to-date have utilized relatively non-specific microbiological assay procedures which are unable to differentiate between concentrations of active erythromycin base and the inactive pro-drug derivatives. A high-performance liquid chromatographic (HPLC) technique is described for the simultaneous determination of erythromycin base and propionate (inactive pro-drug form) in human serum and urine following the oral administration of erythromycin estolate, an acid stable derivative of erythromycin. The method involves a solid-phase extraction step prior to chromatography on a C18 reversed-phase column with coulometric electrochemical detection. Sample handling and storage techniques are presented which minimize hydrolysis of the inactive ester moiety between sample collection and analysis, thereby more accurately reflecting the in vivo situation than in previously published studies. Results from single dose pharmacokinetic studies indicate that only 10-15% of the total erythromycin concentration in vivo is present as the active base component following oral administration of erythromycin estolate. This percentage increases to approximately 25% during multiple dose administration. Novel urinary excretion data are presented which reveal that approximately 40% and 55% of the total erythromycin excreted in urine is excreted as erythromycin base following single and multiple dosages respectively. Computer fitting of mean serum concentration-time data revealed that an open one compartment model with linear first order absorption and elimination best described the absorption and disposition of erythromycin, although poor computer fits for individual data sets were observed. Some evidence of non-linear elimination is presented utilizing both compartmental and non-compartmental pharmacokinetic techniques. Large intra-and inter-personal variability in erythromycin absorption and disposition was experienced which was evaluated in five subjects who each received one 500 mg erythromycin estolate tablet from the same batch, on three separate occasions. In addition. an HPLC method is described for the analysis of "total erythromycin" concentrations following erythromycin estolate administration which involves hydrolysis of the ester component prior to chromatography. as well as an HPLC method utilizing amperometric electrochemical detection capable of monitoring the stability of erythromycin base in stored biological fluids. These methods were uti I ized in various stability studies involving erythromycin base and propionate as well as for the analysis of erythromycin estolate dosage forms.

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