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Biomedical subjects

H S Tan

Publications and source records attributed to H S Tan.

At least 55 records · Page 3Linked to original sources

High-performance liquid chromatographic separation of noreximide and norendimide in bulk material, tablets and animal feed.

Noreximide, a sedative, is generally contaminated to some extent with its endo-isomer, norendimide, which produces excitation. A high-performance liquid chromatographic assay was developed to separate and quantitate these compounds on a 5-microns Ultrasphere ODS column with methanol-water (20:30) as mobile phase and detection at 254 nm. Assay of mixtures of these compounds in bulk material and tablets utilized isoniazide as internal standard. Peak area ratios were linear (r = 0.9999) over 1.4-66.2 micrograms of injected noreximide and 0.2-8.4 micrograms of injected norendimide. Overall percent recovery from simulated tablets containing noreximide alone was 99.6 +/- 0.8% (S.D., n = 3). Overall percent recoveries (+/- S.D.) from tablets containing a mixture of these compounds were 98.9 +/- 0.5% and 102.3 +/- 1.1% for noreximide and norendimide, respectively (n = 3). Noreximide in animal feed for long-term pharmacological studies was isolated by ether extraction and after work up, subjected to the same procedure, except that theophylline was the internal standard. Peak area ratios were linear over 0.2-19.3 micrograms of injected noreximide (r = 0.9999). Overall percent recoveries (+/- S.D., n = 3) of noreximide from spiked animal feed were 97.4 +/- 1.4% and 99.0 +/- 0.5% at the 500- and 5000-ppm levels, respectively. Limits of detection at the 95% confidence level (0.01 a.u.f.s., 20-microliters sample volume injected) were 1.67 microgram/ml and 2.56 micrograms/ml of noreximide and norendimide, respectively, in the final test solution.

Animal Feed↗

A sensitive radioimmunoassay of atrial natriuretic peptide in human plasma, using a tracer with an immobilized glycouril agent.

A highly specific and sensitive radioimmunoassay (RIA) for alpha-human atrial natriuretic peptide (hANP[1-28]) in plasma was developed. The assay used a [125I]monoiodotyrosyl-hANP[1-28] tracer, prepared with an immobilized glycouril agent (Protag) and purified by high pressure liquid chromatography (HPLC), and a highly specific antiserum raised against hANP[1-28], coupled to keyhole limpet haemocyanin, in sheep. Plasma was extracted using C-18 Seppak cartridges. A good parallelism was found after dilution prior to extraction of plasma of patients with congestive heart failure (CHF) or of plasma of healthy subjects. Recovery of hANP[1-28] added to plasma was 96%. The limit of detection was 0.8 pg/tube, intra- and inter-assay variation were 9 and 12%, respectively. Mean plasma ANP values in 25 normal persons with a normal salt intake was 26.0 +/- 15.5 (+/- SD) pg/ml. Plasma levels of 18 subjects (7 normals, 11 CHF) were measured using four different antisera after the extraction step. High correlations were found between the values obtained with these four antisera.

Animals↗

Disposition of nitroglycerin in the beagle dog after intravenous and buccal administration.

The disposition of nitroglycerin was studied in dogs using a crossover design for I.V. (0.85 mg/kg) and buccal (0.75 mg/kg) administration. The pharmacokinetic parameters after I.V. administration are comparable to those in man. The mean values are: t1/2 = 9.2 min; V beta = 3.8 L/kg, Cltot = 238 ml/kg. Similar values were obtained after buccal administration. The bioavailability buccally is 47%. After 7 days pretreatment with nitroglycerin (0.75 mg/kg twice daily, buccally), the area under the I.V. curve (0.85 mg/kg) decreased by about 23%, indicating possible enzyme induction.

Administration, Oral↗

Assay of mixtures of padimate-O and oxybenzone in sunscreen formulations by high-performance liquid chromatography.

A simple assay method for the quality control of some sunscreen products containing padimate-O and oxybenzone has been developed. A methanolic extract of the product containing sulfathiazole internal standard was subjected to reversed-phase high-performance liquid chromatography on a 10-micron Partisil ODS-2 column with methanol-acetonitrile (90:10, v/v) mobile phase. The drug-sulfathiazole peak height ratio was linear between 0.04-2.68 micrograms of padimate-O (r = 1.0003) and 0.02-1.05 micrograms of oxybenzone (r = 0.9997) injected. All peaks were well-resolved. Approximate retention times for sulfathiazole, oxybenzone and padimate-O were 3.9, 5.7 and 7.4 min., respectively. The height equivalent to a theoretical plate (+/- S.D.) were (n = 10) 0.79 +/- 0.07, 0.53 +/- 0.06 and 0.26 +/- 0.04 mm, for sulfathiazole, oxybenzone and padimate-O, respectively. Average percent recoveries (+/- S.D.) (n = 3) from simulated lotions containing 7% padimate-O and 3% oxybenzone were: padimate-O, 101.4 +/- 1.5%; oxybenzone 99.9 +/- 1.9%; from simulated lipsticks containing (a) 7% padimate-O and 3% oxybenzone: 103.8 +/- 1.2% and 100.1 +/- 0.9%, respectively; and (b) 7% padimate-O and 0.5% oxybenzone: 99.4 +/- 0.6% and 99.3 +/- 2.4%, respectively. The method was successfully applied to marketed products.

4-Aminobenzoic Acid↗

Clinical efficacy of sulfadoxine-pyrimethamine in the treatment of falciparum malaria in Sabah, Malaysia.

One hundred and ten consecutive patients with falciparum malaria were treated with Fansidar and primaquine. Of the 61 patients who were followed up at one week, 4 (6.6%) failed to clear their parasitaemia (1 R III and 3 R II treatment failures). Of the subsequent 40 patients who were seen again at one month, another 3 (7.5%) had recrudesced (R I treatment failure). A total of 7 patients thus experienced some form of treatment failure in the cohort of 40 who completed the one month follow up. Only 1 of these 7 patients (with R III treatment failure) failed to respond to repeat Fansidar treatment, and may be the only one with true Fansidar resistance. The overall treatment failure rate of 17.5% (95% confidence interval: 6-29%) in the cohort who completed the study is consistent with the known clinical efficacy of Fansidar. These results suggest no significant Fansidar resistance in falciparum malaria found in Sabah.

Adolescent↗

Assay of mixtures of phenylpropanolamine hydrochloride and caffeine in appetite suppressant formulations by high-performance liquid chromatography.

A simple assay method for the quality control of appetite suppressant products containing phenylpropanolamine hydrochloride and caffeine has been developed. A methanolic extract of the product was evaporated to dryness and the residue was treated with aqueous solutions of sodium metaperiodate and disodium phosphate. Following addition of methyl p-hydroxybenzoate as internal standard and subsequent filtration, an aliquot of the filtrate was subjected to high-performance liquid chromatography on a 10-microns Partisil ODS-2 column with acetonitrile-water (30:70) as mobile phase. The drug: internal standard peak height ratio at 254 nm was linear over the ranges 0.3-2.0 micrograms of phenylpropanolamine hydrochloride and 1.1-16.0 micrograms of caffeine injected. All peaks were well-resolved. The heights equivalent to a theoretical plate (+/- S.D.) for phenylpropanolamine (as benzaldehyde) and caffeine were (n = 10) 0.42 +/- 0.08 and 1.31 +/- 0.23 mm, respectively. Overall per cent recoveries (+/- S.D.) from simulated formulations (n = 6) were 100.7 +/- 1.6% phenylpropanolamine hydrochloride and 99.1 +/- 1.4% caffeine. The method was applied to marketed products and is also applicable for single dose analysis.

Appetite Depressants↗

Intravenous ampicillin pharmacokinetics in the third trimester of pregnancy.

The pharmacokinetics of a single dose of intravenous ampicillin were studied in nine patients during their third trimester of pregnancy. Each volunteer was given either 500 mg (5.7-8.8 mg/kg) or 1 g (15.4-21.4 mg/kg) of sodium ampicillin by rapid infusion. Postinfusion plasma concentration-time curves followed biexponential decay in all subjects. Calculated parameters included a mean plasma distribution volume of 177.1 +/- 97.5 ml/kg, tissue or peripheral distribution volume of 246.2 +/- 143.9 ml/kg, elimination half-life of 1.60 +/- 0.51 h, and total body clearance of 4.59 +/- 1.48 ml/min/kg. Dose-dependent disposition was not observed. Gestation-specific drug therapy research during pregnancy is discussed.

Ampicillin↗

Improved assay for mixtures of citrate and citric acid in systemic alkalizer solutions.

A modification of the USP method for the assay of systemic alkalizer solutions containing mixtures of citrate and citric acid is presented; it involves two titrations and ion-exchange chromatography. A diluted sample is tritiated with 0.02 N NaOH to find the free citric acid content. The eluate from cation-exchange chromatography of an equal volume of diluted sample is titrated with 0.02 N NaOH to assay for total citric acid. Subtracting the results of the first titration from the second provides the citrate content. Synthetic mixtures of potassium citrate-citric acid, potassium citrate-sodium citrate-citric acid, and sodium citrate-citric acid were prepared and assayed. The method was applied to commercially available preparations. The proposed method eliminates some significant errors of the compendial method, and the accuracy and reproducibility are equal or better than those obtained with the compendial method. Theoretically, the result obtained by the compendial method does not necessarily give the citrate content.

Chromatography, Ion Exchange↗

Simultaneous high-performance liquid chromatographic determination of theophylline, ephedrine hydrochloride, and phenobarbital in tablets.

A rapid reversed-phase high-performance liquid chromatographic (HPLC) method was developed for the simultaneous assay of theophylline, ephedrine hydrochloride, and phenobarbital in a tablet matrix. A methanolic extract of the powdered sample containing salicylamide as the internal standard was injected into the chromatograph. The HPLC system used methanol-0.007 M monobasic potassium phosphate (37:63, pH 2.3) as the mobile phase. Detection was at 254 nm, and quantitation was based on the drug-internal standard peak area ratio. This ratio was linear over a concentration range of 20.9-83.5 microgram of theophylline, 4-15.9 microgram of ephedrine hydrochloride, and 1.3-5.1 microgram of phenobarbital. Overall recoveries (+/- SD) from three synthetic tablets were: theophylline, 99.8 +/- 1.3%; ephedrine hydrochloride, 100.2 +/- 0.6%; and phenobarbital, 99.4 +/- 0.7%. The method was compared to the compendial method and also was applied to the assay of commercial tablets containing these three active ingredients. The proposed method is applicable to the assay of individual tablets.

Chromatography, High Pressure Liquid↗

In vitro interaction of quinidine with kaolin and pectin.

The adsorption of quinidine onto kaolin was studied as a function of pH in aqueous solutions in which the ionic strength was adjusted to 0.1. The interaction of quinidine with pectin also was investigated in water and in phosphate buffer; the buffer pH and ionic strength were adjusted to 6.5 and 0.1, respectively. The in vitro results indicated that quinidine was adsorbed onto kaolin. At the highest concentration studied, the extent of adsorption increased from 3.64 mg of quinidine adsorbed/g of adsorbent at pH 2.4 to an average of 5.81 mg/g in the pH 5.5-7.5 range. In the presence of electrolytes, the interaction of quinidine with pectin was relatively small (3-13% bound) as compared to studies performed in water (66-90% bound). The data indicate that some quinidine may be adsorbed when this drug is administered concurrently with kaolin-pectin preparations.

Adsorption↗

High-performance liquid chromatographic determination of azosemide in commercial animal feed.

A high-performance liquid chromatographic (HPLC) method was developed for the assay of 2-chloro-5-(1H-tetrazol-5-yl)-4-[(2-thienylmethyl)amino]benzenesulfonamide (I) in animal feed diet mixtures. The sample is extracted with acetone, an aliquot of the extract is evaporated to dryness, and the residue is dissolved in chloroform. This solution can be subjected to either of two cleanup procedures. The first traps I on a sodium hydroxide-diatomaceuous earth column. Compound I is then recovered using an acetic acid-ethyl acetate-chloroform eluent, which is removed by evaporation, followed by dissolution of the residue in aqueous sodium hydroxide. The second procedure involves the direct extraction of I from the chloroform solution. A linear relationship exists between the HPLC UV detector response at 254 nm and concentration up to 170 microgram/ml. The sodium hydroxide extraction procedure resulted in an overall recovery (+/- SD) of 92.9 +/- 1.6 and 97.4 +/- 1.8% (n = 5) at levels of 200 and 6000 ppm, respectively. Overall recoveries (+/- SD) obtained by the diatomaceous earth column procedure for the 20- and 6000-ppm levels were 90.0 +/- 2.0 and 95.9 +/- 1.6% (n = 5), respectively.

Animal Feed↗

First-pass effect of coumarin in man.

Blood level versus time data upon i.v. and p.o. administration of coumarin in a cross-over study have been analyzed for extent of bioavailability (EBA) and first-pass effect (FPE). In whole blood the parent drug, coumarin (C), and its main metabolite, 7-hydroxycoumarin (7HC), after hydrolysis of the glucuronide were determined. Comparison of the areas under the curve (AUCO leads to infinity) for C and 7HC upon i.v. and p.o. administration revealed that all of the drug is absorbed; however, only approximately 2-6% of C reaches systemic circulation in intact form. Hence, extensive first-pass effect must be assumed. The fraction of unchanged drug reaching systemic circulation predicted from the i.v. study fFPE varied between 0 and 38% assuming a liver blood flow rate (LBF) of 1.53 1/min. When corrected for individual LBF the fPFE varied between 2.5 and 13%. The question whether the FPE is only due to metabolism in the liver or in part due to biotransformation in the intestinal lumen, gut wall and/or portal blood will be the subject of a further paper. It is suspected that C is the pro-drug and 7HC the pharmacologic active moiety.

Administration, Oral↗

Spectrophotofluorometric analysis of 3',4',7-tris[O-(beta-hydroxyethyl)]rutoside in urine.

A sensitive procedure was developed for 3',4',7-tris[O(beta-hydroxyethyl)]rutoside (I) in urine. The method is based on the fluoresence behavior of the I-aluminum complex in absolute methanol. This complex has activation and emission wavelengths of 420 and 480 nm, respectively. Optimum conditions for the reaction were investigated. The fluorescence was linear (r = 0.998) in the range of 0.1-4.0 microgram of I/ml. At concentrations below 0.1 microgram/ml, a shift in the emission wavelength was observed. Replicate studies (n = 9) of spiked urine samples, each containing 0.4 microgram of I/ml, showed good precision with a relative standard deviation of 0.009. Overall percent recovery (+/- SEM) from five urine samples was 99.5 +/- 1.34%. Following a single 500-mg po dose of I to individuals, only traces of I were found in the urine. However, beta-glucuronidase treatment of urine resulted in a total cumulative urine excretion of 26.53 mg of I after 78.6 hr.

Glucuronates↗

Pharmacokinetics of coumarin and its 7-hydroxy-metabolites upon intravenous and peroral administration of coumarin in man.

The pharmacokinetics of coumarin (C) upon i.v. and p.o. administration and its metabolites 7-hydroxy-coumarin (7-HC) and 7-hydroxy-coumarin glucuronide (7-HCG) have been studied. Six healthy volunteers were involved in this investigation. Four of the volunteers participated in a crossover study. Coumarin was administered i.v. and p.o. in dose sizes of 0.25 mg/kg and 0.857 mg/kg, respectively. Coumarin is rapidly absorbed p.o., however the availability to systemic circulation is less than 4%. The rest of the dose appears quantitatively as 7-HC and 7-HCG in systemic circulation suggesting an extensive firstpass effect. Coumarin and 7-HCG are best fitted to an open two-compartment model, whereas 7-HC is best fitted to an open one-compartment model. The biological half-life of both C (0.80 vs. 1.02 h) and 7-HCG (1.47 vs. 1.15 h) was not significantly different for the two routes of administration. The large total clearance of C again suggests a first-pass effect; while that of 7-HCG, which is nearly exclusively eliminated into urine, indicates active tubular secretion of the glucuronide.

Administration, Oral↗

Sensitive assay procedure for ethambutol hydrochloride via charge transfer complex formation.

The charge transfer complex formation between ethambutol and iodine was investigated and utilized as the basis for a sensitive spectrophotometric procedure for ethambutol and its dosage forms. The solutions exhibited blue-shifted iodine bands at 293 and 360 nm. A Job's plot of corrected absorbance against the mole ratio of ethambutol to iodine indicated a 1:2 drug-iodine ratio. At 293 nm, the absorbance was linear (r=0.9998) over the 0.25-15-microgram/ml concentration range, but the concentration range for best accuracy is 1.6-5.8 microgram/ml. The method can be applied successfully to the analysis of commercially available ethambutol tablets.

Chemical Phenomena↗

Colorimetric assay of benzocaine and some dosage forms.

A colorimetric procedure for benzocaine and a number of its dosage forms was developed; it offers improvement in ease, speed, and sensitivity over the official method. The method is based on the formation of a red Schiff base between benzocaine and p-dimethylaminocinnamaldehyde in a nonaqueous acidic medium. At the maximum absorption of 544 nm, the Beer-Lambert law was adhered to over the 0.025--2.5-microgram/ml range. Best accuracy can be obtained for solutions containing 0.25--1.25 microgram/ml. The color was stable for at least 2 hr. Analysis of benzocaine in the dosage forms studied can be directly performed without prior drug extraction.

Benzocaine↗