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Biomedical subjects

G K Shiu

Publications and source records attributed to G K Shiu.

At least 19 recordsLinked to original sources
PubMed1999

Determination of ginsenosides in plant extracts from Panax ginseng and Panax quinquefolius L. by LC/MS/MS.

An HPLC/MS/MS method has been developed for the characterization and quantification of ginsenosides contained in extracts of the root of Panax ginseng (Korean ginsengs) and Panax quinquefolius L. (American ginsengs). The [M + H]+ and [M + Na]+ ions were observed for ginsenoside standards (Rb1, Rb2, Rc, Rd, Re, Rf, Rg1) and four different ginseng extracts. The glycosidic linkages, the core, and the attached sugar(s) of the ginsenosides can be determined from the collision-induced dissociation spectra from the protonated molecules. The relative distribution of these ginsenosides in each extract of American or Korean ginseng was established.

Central Nervous System Agents↗
PubMed1998

Solid-phase extraction-high-performance liquid chromatography determination of verapamil and norverapamil enantiomers in urine.

A simple, rapid, sensitive and selective method has been developed for the stereospecific determination of verapamil and its metabolite, norverapamil in urine. For sample preparation we utilized a membrane-based solid-phase extraction (SPE) disk consisting of a thin, particle-loaded membrane inserted in a plastic syringe-like barrel. The particles, which may be C8 or C18 bonded phase (C8 in this work), are embedded within a matrix of PTFE (Teflon) fibrils. Overall analyte recoveries were above 85%, even at low concentration of 3.0 ng/ml with reproducibilities (C.V. values) below 13.1%. This method of extraction has the advantage of speed and considerable reduction in solvent volumes compared to conventional SPE and solvent extraction. The separation of all the enantiomers was achieved using a single chiral stationary phase column, the cellulose-based reversed-phase, Chiralcel OD-R. Analyte concentrations of less than 3.0 ng/ml could be quantitated with C.V. values below 14%. Calibration curves were linear in the range 2.5-300 ng/ml. Intra-day and inter-day reproducibilities were 10.5-14.2% at 3 ng/ml, 4.8-9.3% at 138.5 ng/ml and 7.8-10.1% at 280 ng/ml level, respectively, for all the enantiomers.

Adult↗
PubMed1994

Resolution of the enantiomers of ibuprofen; comparison study of diastereomeric method and chiral stationary phase method.

In this study, an indirect diastereomeric method and a direct method utilizing a chiral stationary phase (CSP) were investigated for the resolution of ibuprofen enantiomers. In the indirect method, ethylchloroformate (ECF) and 2-ethoxy-1-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) were utilized as first-step derivatizing reagents in acetonitrile or toluene. In the direct CSP method, ibuprofen enantiomers were derivatized to p-nitrobenzyl ureides and then resolved on an (R)-(-)-(1-naphthyl)ethylurea CSP column. The derivatization procedure took place in 10 min with an overall inversion efficiency of 90.3%. Racemization was not observed under the derivatization conditions used. The HPLC-CSP method was utilized to study the pharmacokinetics of ibuprofen enantiomers in dog plasma after a single oral administration of 200 mg of ibuprofen racemate.

Animals↗
PubMed1994

Switching-valve--filter technique for the direct injection and analysis of drugs in plasma using high-performance liquid chromatography.

An automated technique involving switching valves and a filter assembly has been developed and evaluated for the on-line precipitation of proteins and peptides from plasma samples. In the set-up, the proteins were precipitated on-line by injecting the plasma sample into a stream of organic precipitating agent. The precipitates so formed are filtered on-line by a set of filter assemblies consisting of ordinary in-line HPLC solvent filters. Evaluation of the technique was performed using ibuprofen and a mixture of three estrogens, estradiol, equilin and estrone, spiked in dog plasma. The coefficients of variation (C.V.) for system suitability parameters were below 10%. Absolute recovery of ibuprofen in plasma ranged from 80% for 100 micrograms/ml to 114% for 5 micrograms/ml spiked concentrations, respectively. Resolution for equilin and estrone, two closely eluting peaks, was 1.79 (C.V. = 5.8%, n = 7). The switching-valve--filter assembly had no significant effect on the efficiency of the HPLC system.

Animals↗
PubMed1993

Determination of khellin in serum by gas chromatography.

A rapid gas chromatographic assay has been developed for the separation and determination of khellin in human serum. Using a DB-17 capillary column and a simple chloroform extraction, khellin and an internal standard, trioxsalen, were separated from endogenous substances without further clean-up. Spiked serum samples in the range 0.11-1.1 micrograms/ml were assayed and a linear calibration curve obtained.

Chromatography, Gas↗
PubMed1993

Effects of humidity and temperature on in vitro dissolution of carbamazepine tablets.

The rate and extent of dissolution of various approved marketed carbamazepine (CBZ) tablets exposed to 33, 52, 75, and 97% relative humidities at both room temperature and 40 degrees C, and saturated water vapor at room temperature were compared to fresh unstressed tablets. The dissolution data indicate that exposure of CBZ tablets to high humidity and temperature can have a profound effect on tablet disintegration and dissolution. The dissolution rates of some batches of CBZ products exposed to 97% humidity at 40 degrees C or saturated water vapor at room temperature were drastically reduced in only 6-7 days.

Carbamazepine↗
PubMed1992

In vitro release of nitroglycerin from topical products by use of artificial membranes.

An in vitro testing method for measuring the release of nitroglycerin from topical drug products was evaluated. The method involved measuring the amount of nitroglycerin that diffused from ointments and patches through various synthetic membranes into receptor fluid contained in a modified Franz diffusion cell. Plots of the amount of nitroglycerin released against the square root of time for all 10 synthetic membranes were linear. Five membranes (group I) were found to release nitroglycerin at similar rates (difference not significant; p > 0.05). Use of the other five membranes (group II) in diffusion cells resulted in release rates significantly slower than those of group I membranes (p < 0.05). Rapid permeation of nitroglycerin from a solution through a polysulfone membrane demonstrated a lack of significant diffusion barrier properties of this membrane. Rates of release of nitroglycerin from commercially available ointments were found to be similar. A comparison of three commercial nitroglycerin patches revealed that these products released nitroglycerin at different rates in vitro.

Administration, Cutaneous↗
PubMed1991

A new method of dissolution in vitro, the "Bio-Dis" apparatus: comparison with the rotating bottle method and in vitro: in vivo correlations.

The aim was to study a new method of dissolution in vitro, the "Bio-Dis" apparatus, and to compare it with the classical rotating bottle method. Several theophylline controlled-release drug dosage forms were studied. Dissolution testing was performed in increasing pH in standard conditions and after treatment with peanut oil in order to simulate high fat meals and to correlate the in vitro percent dissolved with the in vivo results obtained. The in vivo study was carried out on three groups of healthy volunteers receiving each dosage form in a randomized order just before a high fat breakfast or in the fasting state. The in vitro percent dissolved obtained was compared with those published results obtained with rotating bottles. A linear relationship was established between these results. From the in vivo absorbed percentages calculated according to the Wagner-Nelson method, a linear relation was found between the in vivo percent absorbed and the in vitro percent dissolved in the different conditions. The relationships observed are similar for all the forms under both conditions. The "Bio-Dis" offers advantages over the rotating bottle method. The study reported allows this dissolution apparatus to be proposed as an alternative to the rotating bottle apparatus.

Biological Availability↗
PubMed1991

In vivo-in vitro correlation of salbutamol release from a controlled release osmotic pump delivery system.

The drug release of salbutamol from a controlled release (osmotic pump) tablet was determined in vitro by four different dissolution apparatuses. From published in vivo data, percent of drug absorbed and percent of drug released in vivo were estimated. The highest correlation was obtained between percentage released in vitro versus percentage released in vivo using polynomial regression.

Administration, Oral↗
PubMed1990

Dissolution testing of norethindrone:ethinyl estradiol, norethindrone:mestranol, and norethindrone acetate:ethinyl estradiol combination tablets.

Dissolution of oral contraceptive combination products from six manufacturing firms was studied utilizing the rotating basket method at 100 rpm in 600 mL of 0.1 M HCl and 0.02% sodium lauryl sulfate (SLS). Most of the combination products of norethindrone (NE):ethinyl estradiol (EE) dissolved satisfactorily in water using the paddle method which was first proposed by U.S.P., whereas three of 18 tested products showed better dissolution in acidic aqueous medium containing SLS. Acidic medium with surfactant was also found to be suitable for combination products of norethindrone (NE):mestranol (ME) and norethindrone acetate (NEAc):ethinyl estradiol (EE). A modified U.S.P. assay procedure, a reversed-phase high-performance liquid chromatographic (HPLC) method with a mobile phase of acetonitrile and phosphate buffer, was used to analyze NE and EE concurrently. The NEAc and ME were analyzed separately in these combination products. The NEAc was found to hydrolyze to some extent (approximately 20% in 8 h) in acidic dissolution medium at room temperature, but less so at 4 degrees C. The NE was identified as the sole degradation product of NEAc hydrolysis and was also measured to account for the total amount of NEAc dissolved. A simple dissoluting testing method which utilizes a single dissolution medium was applicable for all oral contraceptive combination tablets surveyed.

1-Propanol↗
PubMed1990

Theophylline-controlled release preparations and fatty food: an in vitro study using the rotating dialysis cell method.

The in vitro dissolution behavior of four controlled-release theophylline products was investigated utilizing the rotating dialysis cell method. The effects of pH, oil, and enzymes on the dissolution profiles were studied. The wide range of pH values and the content of oil and enzymes in the dissolution media in the dialysis cell, which functioned as an in vitro model, were simulated to mimic physiological changes due to food along the entire gastrointestinal tract. Treatment with oil affected the dissolution behavior of Uniphyl and especially Theo-Dur Sprinkle but had little or no effect on the dissolution profiles of Theo-Dur tablets and Theo-24 capsules. The in vitro observations of the oil effect were related to the food effect obtained from published in vivo studies. The rotating dialysis cell can be a useful tool in studying factors which may be responsible for dissolution-related food effects on the absorption of controlled-release products.

Bile Acids and Salts↗
PubMed1989

The beagle dog as an animal model for a bioavailability study of controlled-release theophylline under the influence of food.

Beagle dogs were evaluated as an animal model to study the effect of food on the bioavailability of two commercially available oral controlled-release theophylline products. The products were administered with and without food in single doses, and the bioavailability parameters were compared with those following an i.v. aminophylline dose. The total plasma theophylline clearance in dogs following an i.v. dose was 0.128 liter/hr/kg and the volume of distribution was 0.8 liter/kg using a one-compartment model. The absolute bioavailabilities of these two products under fasting conditions were 31 and 48%, respectively. The food increased the bioavailability of one product and decreased the bioavailability of the other. The overall trends in relative bioavailability of these two products with and without food appeared to be similar to those reported in humans.

Absorption↗
PubMed1988

The effect of food on the absorption of controlled-release theophylline in mini-swine.

The effect of differing fat contents of food on the bioavailability of theophylline following a 400-mg single dose of Theo-24 was studied in mini-swine. The pharmacokinetics of theophylline, following the intravenous administration of aminophylline equivalent to 5 mg/kg as a single dose, were also studied in the same animals. The terminal plasma half-life of theophylline following an i.v. dose was found to be approximately 24 hr. The volume of distribution, Vdext, and clearance following the i.v. dose were approximately 0.7 liter/kg and 0.023 liter/hr/kg, respectively. The terminal half-life of theophylline following the administration of theophylline capsules under fasting conditions was 21 hr. The average bioavailability under fasting conditions was approximately 80% compared to the i.v. dose. Food appeared to have decreased the rate of absorption but no significant effect on the extent of absorption.

Aminophylline↗
PubMed1988

Capillary gas chromatographic (GC) analysis of nitroglycerin and its denitration products in plasma.

A convenient, specific, and sensitive capillary gas chromatographic (GC) assay for analyzing nanogram concentrations of nitroglycerin and its dinitro- and mononitrometabolites in plasma has been developed. Using a bonded-phase (DB-1) 30-m, 1-micron-thick film capillary column and a 1-m, 5-microns-thick film precolumn, separation of nitroglycerin and all four partially nitrated metabolites was achieved in less than 15 min. On-column injection, electron capture detection, and isothermal operation at 100 degrees C yielded a linear extraction curve over a 300-ng/ml range without any need to concentrate sample extracts. Using methyl t-butyl ether as extraction solvent and o-chloronitrobenzene as internal standard, recoveries from plasma spiked at levels greater than 10 ng/ml approximated 35% for the 1-monometabolite, 40% for the 2-monometabolite, and greater than 90% for all others. The method was employed in a pharmacokinetic study of nitroglycerin administered intravenously to beagle dogs. Plasma samples were collected at various time points and analyzed.

Animals↗
PubMed1986

Hemodynamic effects of isoflurane in the newborn piglet: comparison with halothane.

To better understand the mechanism of hypotension and bradycardia that may occur in newborn infants during isoflurane anesthesia, we studied the hemodynamic changes in the major determinants of cardiac output in 15 newborn piglets given 0.5, 1.0, and 1.3 minimal alveolar concentrations (MAC) of isoflurane and in nine sham-instrumented, age-matched control animals. Cardiac output did not differ from the baseline reading or the control group at any isoflurane dose. Mean aortic pressure (MAP) decreased 23-45% in a dose-related manner. Total peripheral resistance index (TPRI) decreased 29% at 0.5 MAC, but did not decline further at higher concentrations. Because the decrease in MAP was offset by a similar reduction in TPRI, cardiac output did not change. Heart rate decreased significantly at 1.3 MAC (-19%). Contractility was depressed at all concentrations: left ventricular dP/dT decreased progressively at 0.5 and 1.0 MAC, and echocardiographic shortening fraction decreased significantly at 1.0 MAC. Left ventricular end-diastolic pressure was not affected. Eight of twelve animals who had bradycardia while breathing isoflurane were atrially paced at their baseline heart rate. Because pacing did not restore MAP, TPRI, and LV dP/dT/DP40 (a contractile index independent of preload and afterload) to control values, bradycardia was not primarily responsible for depression of these variables. At equipotent concentrations, isoflurane reduced MAP and TPRI more than, and cardiac output less than, halothane did in previous studies in this laboratory. Heart rate and dP/dT were decreased to a similar extent by both agents. Blood, heart, and brainstem isoflurane LD:MAC ratios were 2.04, 2.00, and 2.84, respectively, indicating a relatively low margin of safety for isoflurane in young piglets.

Animals↗