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Biomedical subjects

A P Cheung

Publications and source records attributed to A P Cheung.

31 records · Page 2Linked to original sources

Capillary electrophoresis analysis of concanavalin A and its succinyl derivative.

A high-performance capillary electrophoresis (CE) system has been developed for concanavalin A (Con A) and its succinyl derivative (SCA). Under the CE system, the tetramer, trimer, dimer, monomer and protein fragments of CA were separated in less than 50 min. SCA was resolved into more than 10 components which were believed to be isomeric succinyl derivatives of Con A. The CE system is a simple and sensitive analytical technique to profile the composition of Con A and SCA preparations. The minimum concentration of Con A in water detectable by the CE system is 1 microgram ml-1.

Concanavalin A↗

Problems affecting the liquid chromatographic quantitation of chlorhexidine digluconate in ophthalmic solutions.

A liquid chromatogrpahic (LC) assay was recommended by the Food and Drug Administration of the United States for the uptake and release study of chlorhexidine digluconate (CHDG) in ophthalmic solutions by contact lenses. The results from this and other reversed-phase LC assays of CHDG were inaccurate when the working standard and sample solution matrices were different. The error was caused by binding of the analyte onto the container surface and LC column packings. The loss of chlorhexidine due to binding was dependent upon, and very sensitive to, the counter ions in the sample solutions. Relative to water solutions of CHDG, solutions containing chloride, thiosulphate and edetate reduced the loss of the analyte, while solutions containing borate enhanced the loss. To assay CHDG reliably with reversed-phase LC, the media of the working standard and the sample solutions should be closely matched.

Chlorhexidine↗

Partition coefficients and capacity factors of some nucleoside analogues.

The AIDS epidemic has brought into focus the development of antiviral agents, of which nucleoside analogues are an important class. The single most important physico-chemical property of a chemotherapeutic agent is its hydrophobicity. This paper reports the hydrophobicity, determined as log partition coefficient (P) by the shake-flask method, of 25 nucleoside analogues. The capacity factors (k') of these analogues were also obtained by reversed-phase liquid chromatography. There is a very strong linear correlation between the log P and the log k' values of all the nucleoside analogues, indicating that hydrophobicity of nucleosides can be determined by liquid chromatography. Examination of the P data indicates that an empirical mathematical relationship exists between the partition coefficient value and the molecular structure of the nucleoside analogues. A table of constants and an equation is proposed to estimate the P of nucleoside analogues.

Antiviral Agents↗

31P-NMR assay of phosphatidylcholine and phosphatidylethanolamine in AL721.

A 31P-NMR based method has been developed for the assay of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in AL721. The assay is based on the comparison of NMR signal intensities of the phosphatidyl moiety of PC and PE to the signal of triphenylphosphate (TPP), the internal standard. The assay is specific and reliable for the quantitation of phospholipid mixtures. Its uncertainty, due primarily to low intensity of 31P signals, was estimated at less than 6%.

Drug Combinations↗

1H-NMR assay of phosphatidylcholine and phosphatidylethanolamine in AL721.

A 1H-NMR based method has been developed for the assay of phosphatidylcholine (PC), and phosphatidylethanolamine (PE) in AL721. The assay was based on the comparison of NMR signal intensities of the choline and the ethanolamine moiety of PC and PE, respectively, to the signal of imidazole, the internal standard. The assay was reliable and more accurate than the commonly used LC or TLC methods. The uncertainty, due primarily to signal intensities, of the 1H-NMR method was estimated at less than 3%.

Chromatography, Liquid↗

Liquid chromatographic determination of 2',3'-dideoxyguanosine in human plasma.

A rapid assay for 2',3'-dideoxyguanosine (ddG) in human plasma has been developed. The ddG was first extracted from human plasma using solid phase extraction. The extract containing ddG was then assayed with liquid chromatography using an ODS column and a mobile phase of 9% methanol in pH 6.8 phosphate buffer. The overall method had good accuracy (within 2%), linearity (r = 0.9998), sensitivity (LOD = 1.8 ng, S/N = 3) and recovery (greater than 99% for 5-50 micrograms ddG per ml plasma).

Chromatography, Liquid↗

Contaminants in commercial dapsone.

Three contaminants commonly found in commercial dapsone were identified as 2,4'-sulfonylbis(benzeneamine), 4-(phenylsulfonyl)benzeneamine, and 4-(4'-chlorophenylsulfonyl)benzeneamine. The identities were based on the spectral analysis and unambiguous synthesis of each compound. Solvent-free, pure dapsone was prepared by recrystallization from chloroform.

Chemical Phenomena↗

Quantitative capillary electrophoresis and its application to the polyanionic quinobene.

Factors affecting the accuracy of capillary electrophoresis (CE) assays in general are discussed. Methods to improve the reproducibility and reliability of these assays are suggested. The improvements are demonstrated by developed CE assays for quinobene and suramin. The assays were reproducible (RSD < 2%), accurate (error < 2%), and linear over a concentration range of 1-800 micrograms ml-1 (r2 = 0.999).

Antiviral Agents↗

Liquid chromatography and capillary electrophoresis analysis of polyanionic quinobene.

Quinobene is the tetrasodium salt of an organic tetrasulphonic acid. Its unusual solubility characteristics makes the development of LC analysis difficult. However, a specific, precise and accurate LC assay was eventually achieved for quinobene. The assay required gradient elution and was not efficient for quinobene with respect to plate number. As an alternative, a capillary electrophoresis (CE) assay was also developed for quinobene. The CE assay was comparable to the LC assay in precision and accuracy. It was unaffected by the unusual solubility characteristics of quinobene and was more specific, efficient and rugged than the LC assay.

Antiviral Agents↗

Compatibility and stability of bryostatin 1 in infusion devices.

Bryostatin 1 is currently in phase II clinical trial sponsored by the National Cancer Institute as an anticancer chemotherapeutic agent. Bryostatin 1 for injection was supplied in a dual pack containing a drug vial and a diluent vial and was manufactured by Ben Venue Laboratories, Inc (Bedford, OH). The stability and compatibility of the bryostatin 1-PET formulation, diluted to 1 and 10 ug/mL in saline and benzyl alcohol preserved saline, with polypropylene (PP) and polyvinyl chloride (PVC) bags at room temperature (27 degrees C) were studied. All experiments were conducted in triplicate and analyses were performed using a validated, stability-indicating, high performance liquid chromatography (HPLC) assay. Bryostatin 1 solutions were compatible with PP bags. At both concentrations and with both salines, the bryostatin content remained unchanged during the 28-day storage period, benzyl alcohol concentration in the preserved saline solutions also remained relatively constant. In PVC bags, however, a decrease in bryostatin 1 concentrations without generation of decomposition products was observed at both dilutions and with both salines during the 28-day storage. A decrease in benzyl alcohol concentration in the preserved saline was also observed. While no diethylhexylphthalate (DEHP) leakage into the solution was observed in PP bags, DEHP leakage in PVC infusion bags was observed on day 2 of storage which increased with storage time and leveled off on day 6. The amount of DEHP leached into drug solution is dependent on the drug concentration. This study suggests bryostatin-PET formulation diluted with preserved saline can be used for long-term (4 week) intravenous administration using PP infusion bags, but not with PVC bags.

Antineoplastic Agents↗

Cholesterol inhibitory effects on human sperm-induced acrosome reaction.

Progesterone (P4) is known to induce an acrosome reaction in mammalian sperm in vitro, whereas cholesterol is a major inhibitor of acrosome reaction. This study had three objectives: to study the in vitro effects of exogenous cholesterol on acrosome reactions in human sperm, to study the mechanism by which cholesterol affects P4-induced acrosome reaction and those induced by dibutyryl cyclic adenosine monophosphate (db-cAMP), and to study the status of the P4 surface receptor during capacitation and acrosome reaction and its relationship with cholesterol and different acrosome reaction inducers. Acrosome reaction was induced with exposure to 10 microg/mL of P4 for 30 minutes and 1 mM of db-cAMP for 30 minutes in motile sperm either in the presence or absence of 0.1-1 microg/mL of cholesterol for 30 minutes. The effects of a 30-minute exposure to 1 microg/mL of beta-sitosterol, a cholesterol plant analogue, as well as the effects of cholesterol on P4-induced acrosome reactions were compared. Fluorescein isothiocyanate-labeled albumin-progesterone conjugate (P4-FITC-BSA) was used as the probe in order to quantify the percentage of sperm in which the P, surface receptor was exposed. The results of this study indicate that cholesterol inhibited P4-induced acrosome reactions when added to the sperm during capacitation (long incubation) and when it was added with P4 during the induction of acrosome reactions (short incubation). Similarly, acrosome reaction that was induced by db-cAMP was also inhibited by cholesterol. Fifty percent of P4-induced acrosome reaction was inhibited by a cholesterol concentration of 0.2 microg/mL. Cholesterol's inhibition of induced acrosome reaction was independent of P4 concentration. Beta-sitosterol inhibited P4-induced acrosome reaction in a dose-dependent manner that was identical to that of cholesterol. We observed that increases in the P4 surface receptor exposure were time-dependent and receptors migrated toward the equatorial segment during the first 2 hours of capacitation. We also found that db-cAMP induced the appearance of the P4 surface receptor in the sperm plasma membrane and that cholesterol inhibited it. The results of this study suggest that cholesterol inhibits acrosome reaction in a noncompetitive manner by modifying the structure of the sperm plasma membrane, which prevents exposure of the P4 surface receptor for P4 binding.

Acrosome Reaction↗

Clinical approach to female reproductive problems.

Conditions of infertility addressed here include ovulatory dysfunction, tubal and pelvic factors, uterine and cervical factors, immunologic factors, and unexplained infertility. A discussion of recurrent loss of pregnancy and antenatal diagnosis completes the chapter.

Abortion, Habitual↗