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Biomedical subjects

A P Cheung

Publications and source records attributed to A P Cheung.

At least 19 recordsLinked to original sources
PubMed2002

A new sensitive HPLC assay for methoxyamine and its analogs.

Methoxyamine (MOA) and its analogs are polymerization regulators, building blocks and intermediates for agrichemicals and pharmaceuticals. MOA induces mutagenesis of nucleic acids and has been considered for anti-cancer and anti-virus therapy. It has been studied as a DNA repair modifier in anti-cancer therapy. HPLC procedures available in the literature for MOA are all based on electrochemical detection, which is not commonly available. This paper describes the development and validation of a HPLC assay with UV detection for MOA and its analogs. The analytes are first reacted with o-phthalaldehyde to form an oxime derivative before chromatography with an ODS column. Detection is achieved by UV at 254 nm. The chromatography resolves MOA from its decomposition products and analogs. The assay is reproducible (R.S.D. < 0.8%), linear (r(2) = 0.9997), and accurate (error < 1%). The method is sensitive and has a lower detection limit of 5 pmol (0.4 ng of MOA.HCl), which is comparable to that of electrochemical detection.

Chromatography, High Pressure Liquid↗
PubMed2001

High-performance liquid chromatographic analysis for a non-chromophore-containing phosphatidyl inositol analog, 1-((1-O-octadecyl-2-O-methyl-sn-glycero)phospho)-1D-3-deoxy-myo-inositol, using indirect UV detection.

Phosphatidylinositide-3-kinase (PI3 kinase) is an important constituent of growth factor regulation. It is also involved in oncogene signaling pathways. An ether-containing phosphatidyl inositol(PI) analog, OMDPI, 1-[(1-O-octadecyl-2-O-methyl-sn-glycero)-phospho]-1D-3-deoxy-myo-inositol, is a potent inhibitor of this pathway and may be clinically useful in the treatment of a variety of neoplasms. OMDPI is currently being investigated as an anti-tumor agent by the National Cancer Institute, NIH. OMDPI, a non-chromophore-containing PI analog, is not directly adaptable to the commonly used UV detection of HPLC. This paper reports the development and validation of an HPLC assay for OMDPI based on indirect UV detection, in which a UV-absorbing ion-pair reagent (the probe), protriptyline, is added to the mobile phase to induce a signal for the compound. The method is sensitive (limit of detection <5 microl of 1 microg/ml or 5 ng), precise (R.S.D.<2.5%), linear (r2=0.9995) and accurate (error<0.7%). It is superior to refractive index detection and evaporative light scattering detection in either sensitivity or linearity and does not require special equipment.

Chromatography, High Pressure Liquid↗
PubMed2001

Ultrasound and menstrual history in predicting endometrial hyperplasia in polycystic ovary syndrome.

OBJECTIVE: To assess the role of endometrial thickness on vaginal ultrasound assessment and menstrual history in predicting endometrial hyperplasia in women with polycystic ovary syndrome (PCOS) who presented with infertility due to anovulation. METHODS: This was a prospective study in a university referral-based fertility and endocrine clinic. Fifty-six women with PCOS presenting with infertility due to anovulation underwent both vaginal ultrasound assessments and endometrial biopsies. The main outcome measures were the predictive value of sonographic endometrial thickness (primary objective) and the menstrual history with other clinical characteristics (secondary objective) for proliferative endometrium and endometrial hyperplasia in logistic regression analysis. Their predictive value was further examined by receiver operating characteristic curve analysis. RESULTS: Thirty-six PCOS patients (64.3%) had proliferative endometrium and 20 (35.7%) had endometrial hyperplasia. Five of the latter (25%) had cytologic atypia. Endometrial thickness less than 7 mm or intermenstrual interval less than 3 months (corresponding to more than four menstrual periods yearly) was associated with proliferative endometrium only. The endometrial thickness correlated positively with endometrial hyperplasia (P =.018) and, together with the average intermenstrual interval, were significant predictors of endometrial hyperplasia (P <.001). CONCLUSION: These findings point to the usefulness of obtaining a detailed menstrual history in women with PCOS by identifying those at increased risk of endometrial hyperplasia and who require an endometrial biopsy. The endometrial thickness corroborates this clinical impression and is particularly useful when the menstrual history is uncertain. Endometrial hyperplasia in this population is effectively excluded when the endometrial thickness is less than 7 mm.

Adult↗
PubMed2001

Stability-indicating HPLC assay and solution stability of a new diaziridinyl benzoquinone.

RH1, 3-methyl-6-hydroxymethyl-2,5-diaziridinyl-1,4-benzoquinone, is a NQO1 (NAD(P)H quinone oxidoreductase) directed anti-tumor agent. It is designed as a water soluble analog of MeDZQ (3,6-dimethyl-2,5-diaziridinyl-1,4-benzoquinone) and is a drug candidate for clinical evaluation. A HPLC assay has been developed for its analysis. The assay is sensitive (ldl<0.2 ng), precise (rsd<1%), linear (r(2)=0.9997), accurate (error<0.6%), and stability-indicating. Using the developed assay, aqueous stability of RH1 has been evaluated. Both aziridine rings in MeDZQ are known to be easily hydrolyzable in aqueous solutions, however, hydrolysis of the second aziridine ring in RH1 appears inhibited.

Aziridines↗
PubMed2000

Acute effects of estradiol and progesterone on insulin, lipids and lipoproteins in postmenopausal women: a pilot study.

OBJECTIVES: To examine the acute effects of estradiol-17beta (E(2)) and progesterone (P) on serum levels of insulin, lipids and lipoproteins in estrogen-deficient postmenopausal women, whereby, a direct cause-effect relationship could be established without the influence of lifestyle changes. MATERIALS AND METHODS: Nine postmenopausal women were given oral E(2) (Estrace) 2 mg/day for 28 days and oral micronized P (Prometrium) 200 mg/day in the last 14 days of E(2) treatment. Fasting blood samples were obtained before starting E(2) (day 1) and P (day 15) and on day 29. Serum levels of insulin, triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and lipoprotein (a) (Lp(a)) at the three time points were compared by Friedman analysis of variance (ANOVA). Corresponding levels of glucose, the apolipoproteins (Apo) A1 and B and serum androgen levels were also evaluated. RESULTS: E(2) decreased while P increased fasting levels of insulin (32.45+/-3.57, 26.36+/-2.90 and 37.36+/-3.67 pmol/l on day 1, 15 and 29 respectively; P<0.01). Fasting glucose to insulin ratios changed inversely (P<0.01). E(2) increased HDL from 1.07+/-0.05 mmol/l on day 1 to 1.17+/-0.07 mmol/l on day 29 but decreased corresponding levels of Lp(a) from 261+/-93 to 211+/-83 U/l (P=0.03 for both). TC and LDL levels fell significantly after 14 days of E(2) treatment with no further decrease when P was added. Androgen levels remained unchanged during hormone treatment. CONCLUSION: The sequential, acute effects of E(2) and micronized P on insulin and lipids confirm a direct cause-effect relationship. The acute effects of P on insulin in particular, highlights the importance of standardizing the medication days according to estrogen and progestin in the clinical evaluation of their true metabolic impact in longer-term studies and may influence the choice of progestin type, dose and duration in hormone replacement.

Blood Glucose↗
PubMed2000

Stability-indicating high-performance liquid chromatographic assay and analysis of decomposition products of 2-[4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy]propanoic acid.

A stability-indicating HPLC assay has been developed for 2-[4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy]propanoic acid (XK469). XK-469 is the 7-chloro analog of herbicide Quizalofop and is currently under development as an antineoplastic agent. HPLC separation of XK469 is achieved with an ODS column using isocratic elution of an aqueous MeOH mobile phase. The assay is reproducible (RSD=0.9%), linear (r2=0.999), accurate (error=1.2%) and sensitive (LDL=1.2 ng). The HPLC separates XK469 from its forced decomposition products. Identities of the decomposition products have been elucidated.

Chromatography, High Pressure Liquid↗
PubMed2000

Enantiomeric separation of an aryloxyphenoxypropanoic acid by CE and LC.

A capillary electrophoresis (CE) and an high performance liquid chromatography (HPLC) chiral separation have been developed for an aryloxyphenoxypropanoic acid, 2-[4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy]propanoic acid, a new antitumor agent. The racemic mixture is analyzed, without derivatization, as the free acids. The CE assay is based on inclusion complexation with hydroxypropyl-beta-cyclodextrin. HPLC separation is achieved with a CSP column with the glycopeptide, teicoplanin, as the chiral selector. Both methods give baseline resolution to the R-and S-isomers. The methods were validated for assay and for optical purity assessment of the R-isomer. For assay, the HPLC method is precise (RSD < 0.6%), accurate (error, 0.5%) and linear (r2 = 0.9998). It is able to precisely (RSD = 0.5%) and accurately (error, 0.9%) detect 0.3-6.0% of one isomer (S) in the other (R). The CE assay is much less precise and accurate than HPLC. It is a good alternative to separate and detect the enantiomers, however.

Antineoplastic Agents↗
PubMed2000

Stability-indicating LC assay of and impurity identification in homoharringtonine samples.

Homoharringtonine (HHT) is a potent myelosuppressive agent and has antitumor activity. Recent studies suggest that it inhibits tumor growth by inducing apoptosis. HHT is an ester of the alkaloid cephalotaxine. It is isolated from genus Cephalotaxus. At least ten HHT analogs have been identified from cephalotaxus extracts. High performance liquid chromatography (HPLC) separations of the cephalotaxine alkaloids in plant extracts have been reported, they have not been validated as specific and stability-indicating for HHT. Due to the complexity of the alkaloid extracts, it is conceivable that additional analogs may still be unresolved from HHT. This paper presents an improved and validated HPLC assay for HHT. The assay is stability-indicating, precise (R.S.D. < 1%), linear (r2 = 0.9999), and accurate (error < 1%). The assay reveals three congeners present as impurities in HHT samples. Two are new and have not been previously reported. Identities of the impurities and forced decomposition products, elucidated with their HPLC retention and spectral data, are also presented.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Pulsatile gonadotrophin secretion in women with polycystic ovary syndrome after gonadotrophin-releasing hormone agonist treatment.

In polycystic ovary syndrome (PCOS), increased luteinizing hormone (LH) pulse frequency has been attributed to either the hypothalamic gonadotrophin-releasing hormone (GnRH) pulse generator or ovarian oestrogen feedback. To address this issue, a detailed examination of pulsatile LH secretion was undertaken during recovery from GnRH agonist (GnRHa) suppression. Each of six women with PCOS and six normal ovulatory women received daily GnRHa treatment for 14 weeks. Frequent blood samples were collected and assayed for gonadotrophins, androgens and oestrogens before, during and up to 4 weeks after treatment. Women with PCOS had higher basal LH pulse frequency and amplitude and increased serum concentrations of LH, androstenedione, testosterone and oestrone than controls. After 3 months of GnRHa treatment, all these parameters were suppressed with no differences observed between the two groups. One week after cessation of GnRHa, LH pulse frequency promptly returned to pre-treatment range with no between-group differences noted, whereas LH pulse amplitude, serum gonadotrophins and ovarian steroids remained maximally suppressed and equivalent in the two groups. Subsequent LH pulse frequency remained constant while LH pulse amplitude and circulating concentrations gradually increased in parallel with a return of serum oestrogen to pre-treatment values. Despite comparable resumption of LH secretion in the two groups, corresponding androgen concentrations in women with PCOS were greater than those of normal ovulatory women. Thus, the immediate restoration of LH pulse frequency after discontinuing GnRHa treatment is largely independent of ovarian oestrogen production and reflects primacy of the GnRH pulse generator in determining basal LH pulse frequency. Equivalent LH pulse frequency rates in the two groups during the recovery period do not suggest an intrinsic hypothalamic-pituitary hyperactivity in PCOS.

Adult↗
PubMed1996

New stability-indicating high performance liquid chromatography assay and proposed hydrolytic pathways of chlorhexidine.

Chlorhexidine (CHD) is an antiseptic agent widely used in mouth rinses and ophthalmic solutions. Its assay in these solutions has been commonly performed with high performance liquid chromatography (HPLC). Published HPLC assays were unable to detect the many possible hydrolysis products of CHD, with the exception of p-chloroaniline. This raises concerns regarding the stability-indicating capabilities of the HPLC assays. In addition, the reliability of these assays was affected by the irreversible absorption of CHD on silica-based reversed phase (RP) columns. Special attention must be paid to the mobile phase or sample matrices in order to obtain reliable assay results. This paper presents a polymer-based RP-HPLC method that is stability-indicating. The method detected six UV-absorbing hydrolysis products of CHD. The identities of the products, which were elucidated by UV and mass spectral analyses, are consistent with the proposed hydrolytic pathways of CHD. Quantitation problems observed with silica-based RP-HPLC assays do not arise with the new method. Preliminary data indicate that the new HPLC method can be developed into a reliable, stability-indicating assay for CHD in ophthalmic solutions.

Anti-Infective Agents, Local↗
PubMed1995

Precision in capillary electrophoresis with respect to quantitative analysis of suramin.

Suramin is an important anti-tumor and anti-viral chemotherapeutic agent. We have previously presented a capillary electrophoresis (CE) method for its quantitative analysis, where its quantitation was linear over three orders of magnitude, with good precision (1.8%) and accuracy. The constantly varying electroosmotic properties of the capillary due to various causes such as analyte adsorption to the inner wall, affect the migration times of analytes during consecutive electrophoresis runs. This results in progressive changes in analyte peak areas, causing less desirable or unacceptable CE assay precision. This paper illustrates a strategy to overcome the problem of assay reproducibility by using an internal standard whose migration time is short and close to that of the analyte so that the relative change of migration time is minimized. Assay precisions as good as 0.3% were observed in these experiments. These results are in agreement with the theoretical basis of experimental capillary electrophoresis.

Antineoplastic Agents↗
PubMed1995

Application of HPLC and CZE to the analysis of polyoxometalates.

Polyoxometalates (POM) are polymers of transition metal oxides. They are widely used as analytical reagents and reaction catalysts. Some have anti-viral properties and are being investigated as anti-HIV agents. Due to solubility and stability limitations, separation methods for POM are rare in the literatures. This paper presents a HPLC and a CZE method for the analysis of sodium tungstate, its equilibrium products and isopolyanions. The methods are simple and sensitive, and can be used to monitor the purity, stability and solution equilibria of POM.

Chromatography, High Pressure Liquid↗
PubMed1995

Pituitary responsiveness to gonadotrophin-releasing hormone agonist stimulation: a dose-response comparison of luteinizing hormone/follicle-stimulating hormone secretion in women with polycystic ovary syndrome and normal women.

In polycystic ovary syndrome (PCOS), the mechanism responsible for abnormal gonadotrophin secretion, elevated serum luteinizing hormone (LH) and normal or low follicle-stimulating hormone (FSH) concentrations has not been elucidated. One proposed mechanism, as suggested by previous studies, is an augmented sensitivity of pituitary LH release and a corresponding insensitivity of pituitary FSH release to gonadotrophin-releasing hormone (GnRH) agonist stimulation. This study was designed to further compare gonadotrophin responses to GnRH agonist stimulation within and between individual patients in a dose-response manner. Each of six PCOS and six normal ovulatory women was administered a single s.c. injection of the GnRH agonist [(imBzl)D-His6, Pro9-NEt]-GnRH (D-His) at a dose of 0.01, 0.1, 1 and 10 micrograms/kg on four separate occasions. Blood samples were obtained over a 72 h period following D-His administration. Gonadotrophin responses were measured by (i) the maximal rise from pretreatment baseline values (delta max); (ii) the maximal percentage change from baseline (%delta max); and (iii) the integrated response (mean of the cumulative sum of deviations from baseline). Within-group and between-group dose-responses were compared by two-factor analysis of variance and further characterized using the 'Flexifit' computer program. Our results showed that in both groups, progressive increases of LH and FSH occurred following D-His at doses of 0.01 and 0.1 microgram/kg. Further increases beyond the 0.1 microgram/kg dose were not observed. In PCOS women, delta max and integrated response for LH were significantly greater than those of normal subjects at each dose tested. %delta max of LH was significantly lower in PCOS, reflecting higher pretreatment baseline LH concentrations in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

A cost-effectiveness analysis of hormone replacement therapy in the menopause.

OBJECTIVE: To evaluate the cost-effectiveness of hormone replacement therapy in the menopause with particular reference to osteoporotic fracture and myocardial infarction. DESIGN: The multiple-decrement form of the life table was the mathematical model used to follow women of age 50 through their lifetime under the "no hormone replacement" and "hormone replacement" assumptions. Standard demographic and health economic techniques were used to calculate the corresponding lifetime differences in direct health care costs (net costs in dollars) and health effects ("net effectiveness" in terms of life expectancy and quality, in "quality-adjusted life-years"). This was then expressed as a cost-effectiveness ratio or the cost ($) per quality-adjusted life-year (QALY) for each of the chosen hormone replacement regimens. SETTING AND PATIENTS: All women of age 50 in New South Wales, Australia (n = 27,021). RESULTS: The analysis showed that the lifetime net increments in direct medical care costs were largely contributed by hormone drug and consultation costs. Hormone replacement was associated with increased quality-adjusted life expectancy, a large percentage of which was attributed to a relief of menopausal symptoms. Cost-effectiveness ratios ranged from under 10,000 to over a million dollars per QALY. Factors associated with improved cost-effectiveness were prolonged treatment duration, the presence of menopausal symptoms, minimum progestogen side effects (in the case of oestrogen with progestogen regimens), oestrogen use after hysterectomy and the inclusion of cardiac benefits in addition to fracture prevention. CONCLUSIONS: Hormone replacement therapy for symptomatic women is cost-effective when factors that enhance its efficiency are considered. Short-term treatment of asymptomatic women for prevention of osteoporotic fractures and myocardial infarction is an inefficient use of health resources. Cost-effectiveness of hormone replacement in asymptomatic women is dependent on the magnitude of cardiac benefits associated with hormone use and the treatment duration.

Cost-Benefit Analysis↗
PubMed1992

Granulosa cells of polycystic ovaries: are they normal or abnormal?

Understanding whether granulosa cells are normal or abnormal in women with polycystic ovary syndrome (PCO) could have clinical importance. For this purpose, we compared the ability of normal and PCO granulosa cells to synthesize oestrogen and progesterone in vitro in response to follicle stimulating hormone (FSH) and/or insulin-like growth factor-I (IGF-I). The normal granulosa cells were from a 7 mm dominant follicle from a women with regular menstrual cycles. The PCO granulosa cells were from 5-7 mm follicles of three patients who had classical PCO. Several interesting points emerge from the comparison: in each PCO patient there was a high level of bioactive FSH in the follicular microenvironment (greater than or equal to 5 mIU/ml; greater than or equal to 250 ng/ml). This is paradoxical because the concentration of steroids in follicular fluid suggests that PCO follicles are highly atretic and therefore should not contain detectable FSH activity. The capacity to secrete progesterone when challenged with a maximally effective dose of FSH and/or IGF-I, was markedly reduced (8- to 10-fold) in PCO compared to normal granulosa cells. This is in sharp contrast to the oestradiol responses which were much the same for PCO and normal granulosa cells. Also, the time course and dose-response effects of FSH showed some major differences between normal and PCO cells, that is, PCO cells lost their capacity to produce oestradiol when treated continuously with a maximally effective dose of FSH. They were also significantly more sensitive to FSH and failed to become more sensitive to IGF-I when treated with FSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1991

Chiral separation of glycyrrhetinic acid by high-performance liquid chromatography.

An HPLC separation of the 18 alpha and 18 beta diastereomers of glycyrrhetinic acid (GA) has been developed. The separation was achieved with a chiral column (Merck ChiraSpher, Darmstadt, Germany) and a methanol-water (65:35, v/v) mobile phase. The separation is excellent, having a resolution factor of 2.3. The HPLC method is efficient and accurate for the optical purity determination of 18 alpha- and 18 beta-GA samples. The run time is less than 30 min. Quantitation is linear with a lower detection limit of 0.2% for one isomer in the presence of the other. Addition of 0.2% acetic acid to the water in the mobile phase improved the ruggedness of the system without affecting the resolution of 18 alpha- and 18 beta-GA. This modification also allowed partial separation of 18 alpha- and 18 beta-glycyrrhizin, precursors of the GA isomers.

Chromatography, High Pressure Liquid↗