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Class of 2012 Abstract / Specific Aims: To assess the chemical stability of ampicillin for injection in normal saline at pH values ranging from 5 to 6. Methods: A stability-indicating high performance liquid chromatography (HPLC) method was developed and used to determine the stability of ampicillin for injection in normal saline following buffering with sodium acetate and acid adjustment with HCl at pH values of 5, 5.5, and 6. To confirm that the assay was stability-indicating, ampicillin trihydrate reference standard (1 mg/mL) was exposed to alkali, acid, and oxidative stress conditions and analyzed by HPLC for the presence of degradation products. Analysis was performed on a reverse-phase (C-18) column with a mobile phase consisting of water, acetonitrile, 1 M monobasic potassium phosphate, and 1 N acetic acid (909:80:10:1). Other HPLC parameters were: flow rate 1 mL/min; detection wavelength 254 nm; injection volume 20 μL; column temperature 30 ̊C. The method was evaluated for linearity, precision, and accuracy. The chemical stability of ampicillin for injection (18 mg/mL) in normal saline and sodium acetate (pH adjusted at values of 5, 5.5, and 6) was assessed at baseline (t=0), 7, 11, 17, 31, and 44 hours and compared to a control solution (no pH adjustment). Measurements at each time interval were performed in triplicate. Main Results: Ampicillin trihydrate reference standard (1 mg/mL) was adequately separated from degradation products following exposure to alkali, acid, and oxidative stress conditions. After 16 hours, a precipitate was observed in the solution at pH 6, and therefore stability is not reported. All other solutions (pH 5, pH 5.5, and control) were stable for at least 24 hours at room temperature and yielded t90 values of 110, 64.2, and 27.5 hours, respectively. Conclusions: Adjustment of intravenous ampicillin solutions to pH values of 5 or 5.5 significantly increased stability. Ampicillin appears to be most stable at a pH near its isoelectric point (pH 5).

Class of 2009 Abstract / OBJECTIVES: The purpose of this study was to examine solutions of midazolam at a concentration of 1 mg/ml in 2 different types of IV bags while being stored under different conditions to see if they maintain stability over a one month period. METHODS: Triplicate solutions of midazolam 1 mg/ml were made in polyolefin and polyvinyl chloride IV bags and stored under refrigeration, exposed to light at room temperature, and protected from light in amber bags at room temperature. High performance liquid chromatography was used to evaluate solution stability over a 4 week period. RESULTS: All solutions remained stable with no statistically significant (p = 0.164) change in concentration from initial over the four week period. Storage condition also did not have an impact on stability and neither did type of plasticizer used. CONCLUSIONS: Solutions remain stable for longer than the manufacturer stated 24 hours and may be made in advance and stored for future use.

by Wong Kwok Kong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 163-184). / Abstract --- p.2 / Preface / Acknowledgements --- p.6 / List of abbreviations --- p.7 / List of Tables --- p.8 / List of Figures --- p.13 / CONTENTS --- p.16 / Chapter Chapter One： --- Introduction --- p.23 / Chapter Chapter Two： --- Review of pharmacology of propofol --- p.26 / Chapter 1： --- Chemistry structure-Activity relationship --- p.27 / Chapter 2: --- Pharmacokinetics --- p.28 / Chapter 2.1： --- Distribution --- p.29 / Chapter 2.2： --- Elimination --- p.30 / Chapter 2.3: --- "Effects of age, sex, and hepatic and renal disease on the pharmacokinetics of propofol" --- p.35 / Chapter 2.3.1： --- Effects of age / Chapter 2.3.2： --- Effects of sex / Chapter 2.3.3: --- Effects of renal and hepatic disease / Chapter 3: --- Pharmacodynamic --- p.38 / Chapter 3.1： --- Anaesthetic concentrations --- p.38 / Chapter 3.2: --- Recovery characteristics --- p.39 / Chapter 3.3： --- Effects on the cardiovascular system --- p.40 / Chapter 3.4： --- Effects on the respiratory system --- p.43 / Chapter 3.5： --- Effects on cerebral blood flow and intracranial pressure --- p.44 / Chapter 3.6： --- Other effects --- p.45 / Chapter 3.6.1： --- Effects on liver function / Chapter 3.6.2： --- Effects on renal function / Chapter 3.6.3: --- Effects on coagulation / Chapter 3.6.4： --- Effects on adrenal steroidgenesis / Chapter 3.7： --- Side effects --- p.47 / Chapter 3.7.1： --- Pain on injection / Chapter 3.7.2: --- Excitatory & respiratory / Chapter 3.7.3: --- Nausea and vomiting / Chapter 3.7.4： --- Bradycardia / Chapter 3.7.5: --- Anaphylaxes / Chapter 4: --- Clinical use --- p.51 / Chapter 4.1： --- Anaesthesia induction --- p.52 / Chapter 4.2: --- Anaesthesia maintenance --- p.53 / Chapter 4.3: --- Use in sedation --- p.57 / Chapter Chapter Three ： --- Analytical Technique:Propofol content analysis --- p.58 / Chapter 1: --- Introduction high-pressure liquid chromatography --- p.58 / Chapter 2: --- Methods of propofol content analysis --- p.61 / Chapter 2.1: --- Reagents and solutions --- p.61 / Chapter 2.1.1: --- Sodium dihydrogen phosphate / Chapter 2.1.2： --- Cyclohexane / Chapter 2.1.3: --- Tetramethylammonium Hydroxide Solution / Chapter 2.1.4： --- Acetonitrile / Chapter 2.1.5: --- Acetic acid / Chapter 2.2: --- Standard solution --- p.62 / Chapter 2.2.1: --- Propofol standards / Chapter 2.2.2： --- Internal standard / Chapter 2.2.3： --- Control standard / Chapter 2.3： --- Mobile phase --- p.63 / Chapter 2.4： --- High-pressure liquid chromatography --- p.63 / Chapter 2.5: --- Quantification --- p.64 / Chapter 2.6： --- Procedure --- p.67 / Chapter 2.7： --- Throughput --- p.69 / Chapter 2.7.1： --- Fist working day / Chapter 2.7.2: --- Second working day / Chapter 2.7.3： --- Third working day / Chapter 2.7.4: --- Fourth working day / Chapter 2.7.5： --- Fifth working day / Chapter 3: --- Results of propofol content analysis --- p.71 / Chapter 3.1: --- Calibration standard of propofol (Linearity) --- p.71 / Chapter 3.2： --- Control standard of propofol --- p.74 / Chapter 3.2.1： --- Reproducibility / Chapter 3.2.2: --- Recovery / Chapter 3.2.3： --- Stability / Chapter 4: --- Discussion of propofol content analysis --- p.80 / Chapter 4.1： --- Calibration standard of propofol --- p.80 / Chapter 4.2: --- Precision and accuracy of analytical method --- p.86 / Chapter 4.3： --- Extraction efficiency of analytical method --- p.87 / Chapter 4.4： --- Stability of analytical met --- p.89 / Chapter Chapter Four： --- Analytical technique： Protein binding of propofol --- p.91 / Chapter 1: --- Introduction protein binding of propofol --- p.91 / Chapter 1.1: --- Ultrafiltration --- p.92 / Chapter 1.2： --- Equilibrium dialysis --- p.92 / Chapter 2: --- Methods of protein binding of propofol --- p.94 / Chapter 2.1： --- Material & Solution --- p.94 / Chapter 2.1.1: --- Dialysis buffer / Chapter 2.1.2: --- Molecularporous Dialysis Membrane / Chapter 2.2: --- Equilibrium dialysis --- p.96 / Chapter 2.3： --- Determine the optimum dialysis time to reach equilibrium --- p.97 / Chapter 2.3.1： --- Material / Chapter 2.3.2： --- Procedure / Chapter 3: --- Results of protein binding of propofol --- p.99 / Chapter 3.1： --- Results for optimum dialysis time to reach equilibrium --- p.99 / Chapter 3.2： --- Results for reproducibility --- p.101 / Chapter 3.2.1: --- Intraassay coefficient of variation (One analysis day) of propofol in plasma and in protein binding / Chapter 3.2.2: --- Interassay coefficient of variation (Seven analysis days) of propofol in plasma and in protein binding / Chapter 3.3: --- Results for recovery of propofol in plasma and in protein binding --- p.106 / Chapter 3.3.1: --- Recovery of propofol (unheated samples) / Chapter 3.3.2: --- Recovery of propofol (samples heated at 37°C) / Chapter 3.3.3: --- Recovery of propofol (after dialysis at 37°C) / Chapter 3.4： --- Results for stability of propofol in plasma --- p.112 / Chapter 4: --- Discussions of protein binding of propofol --- p.114 / Chapter 4.1: --- Optimum dialysis time to reach equilibrium --- p.114 / Chapter 4.2: --- Discussion for Intraassay & Interassay coefficient of variation of propofolin plasma and in protein binding --- p.114 / Chapter 4.3： --- Recovery of propofol in plasma and in protein binding --- p.116 / Chapter 4.4： --- Discussion for stability of propofolin plasma --- p.118 / Chapter Chapter Five： --- Clinical application of pharmacokinetic studies --- p.119 / Chapter 1: --- Introduction pharmacokinetic model controlled infusion / Chapter 1.1： --- Theoretical basis --- p.119 / Chapter 1.2: --- Use of computer & appropriate pump --- p.123 / Chapter 2: --- Results of propofol pharmacokinetic studies --- p.124 / Chapter 2.1: --- Sample prepare --- p.124 / Chapter 2.2: --- Computer control infusion of propofol according to pharmacokinetic model --- p.126 / Chapter 2.3: --- Comparison of measured and predicted blood concentrations of propofol --- p.129 / Chapter 2.4: --- Test the new paediatric pharmacokinetic model (the revised paediatric rate constants) --- p.136 / Chapter 3: --- Discussion of propofol pharmacokinetics studies： Infusion for Chinese children --- p.141 / Chapter Chapter Six： --- Clinical application on protein binding studies --- p.143 / Chapter 1: --- Plasma proteins and drug binding --- p.143 / Chapter 2: --- Methods of propofol protein binding studies --- p.145 / Chapter 2.1： --- Blood sample acquisition --- p.145 / Chapter 2.2: --- Population characteristics --- p.145 / Chapter 2.3： --- Methods of protein binding assay --- p.145 / Chapter 3: --- Results of propofol protein binding --- p.146 / Chapter 4: --- Discussion of propofol protein binding --- p.153 / Chapter 4.1: --- Protein binding of propofol in Chinese children --- p.154 / Chapter 4.2： --- Protein binding of propofol in pregnant women & neonate --- p.155 / Chapter Chapter Seven： --- Conclusions --- p.158 / References --- p.163 / Appendix --- p.180

Lim Thiam Aun. / Thesis (M.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (p. 142-154). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

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Invasion of renal cell carcinoma into the renal vein has a detrimental effect on the prognosis as this is an important tumour dissemination route. Determination of renal vein invasion is vital to accurate pathological staging. The purpose of this study is to determine if perfusing with formalin and probing the veins of radical nephrectomy specimens allows for easier visualization of the veins and an improved diagnosis of vascular invasion. In this study, 28 radical nephrectomy specimens were examined using renal vein probing and perfusion techniques. The tumours were segregated based on size, Fuhrman grade and tumour type. Comparison of the study tumours versus renal tumours examined in 2009 that were not perfused and probed were based on these groupings. There was a trend to identifying more renal vein invasion, especially for tumours 4.1 to 7.0 cm in diameter, but this did not result in statistical significance in this small study group.

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