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Biomedical subjects

J R Watson

Publications and source records attributed to J R Watson.

At least 19 recordsLinked to original sources
PubMed1995

Fluconazole therapy in a rhesus monkey (Macaca mulatta) with epidural Trichosporon beigelii in a cephalic recording cylinder.

An adult female rhesus monkey with a cephalic recording cylinder surgically implanted over a craniotomy site developed cloudy cylinder fluid and a white gelatinous plaque on the epidural capsule surface. Results of baseline hematologic, serum biochemical, and cerebrospinal fluid analysis and simian retrovirus panel were unremarkable. Aerobic culture of the cylinder fluid yielded a pure culture of Trichosporon beigelii. This organism is a ubiquitous saprophytic fungus that is a potential pathogen, especially in the immunocompromised host. Factors that could have contributed to the infection included a microenvironment in the cylinder that was favorable to fungal growth, and presence of a dural pseudocapsule of collagen and granulation tissue in the implant which could have inhibited cellular defense mechanisms. An intravenous formulation of fluconazole was selected for direct application into the recording cylinder on the basis of safety and efficacy. Fluconazole is a highly water-soluble, metabolically stable bis-triazole antifungal with excellent cerebrospinal fluid penetration and low toxicity. A 4-week course of treatment eliminated Trichosporon organisms from the cylinder. Change to oral administration of fluconazole was made at that time to allow use of cephalic cylinder antibiotics that are incompatible with fluconazole. Further treatment with fluconazole was continued orally for 3 more months to prevent fungal recrudescence. Culture of cylinder fluid was performed periodically for 6 months after resolution, and results remained negative for T. beigelii. This case is believed to be the first reported T. beigelii infection in a non-human primate. Fluconazole was effective in eliminating the infection from the cylinder and preventing its recurrence.

Animals↗
PubMed1991

Kinetic study of serum gentamicin concentrations in baboons after single-dose administration.

This study establishes preliminary pharmacokinetic data on the use of gentamicin sulfate administered IM to baboons. Serum concentrations greater than or equal to 12 micrograms/ml are generally agreed to cause toxicosis in human beings. On the basis of preliminary test results suggesting that the manufacturer's recommended dosage for dogs of 4.4 mg/kg of body weight caused potentially toxic serum concentrations, a dosage of 3 mg/kg was chosen to conduct a single-dose kinetic study in 6 baboons. Using a single-compartment model, the gentamicin serum half-life for IM administration of 3 mg of gentamicin/kg was 1.58 hours, and serum concentrations remained below the potentially toxic concentrations reported for human beings. We suggest that a dosage of 3 mg/kg is safer than a dosage of 4.4 mg/kg administered IM to baboons. Minimal inhibitory concentrations for 2 Pseudomonas aeruginosa isolates were less than or equal to 1 micrograms/ml. On the basis of our measured elimination half-life of 1.58 hours, it is reasonable to suppose that dosing q24 h will be inadequate to maintain therapeutic serum concentrations. We calculate that serum concentrations will remain at or above our measured minimal inhibitory concentration for P aeruginosa (1 micrograms/ml) for 100% of the treatment time if the animal is dosed q 6h, 78% for dosing q 8h, and 52% for dosing q 12h. Therefore, we suggest 3 mg/kg, q 8h or q 6h as appropriate dosing schedules for the use of gentamicin sulfate administered IM to baboons.

Animals↗
PubMed1984

Gas chromatographic method for solvent residues in drug raw materials.

A gas chromatographic (GC) method for screening drug raw materials, soluble in aqueous media, for volatile solvent residues has been developed. After dissolution, separate portions of the drug are each separately extracted with n-octane, toluene, and ether and injected into a chromatograph equipped with a porous polymer column and a flame ionization detector. The range of extractant polarities provides chromatograms which, taken together, are free of interfering peaks from 0 to approximately 20 min. Peaks due to solvent residues in the drug are identified by retention time with confirmation of identity by GC-MS.

Chemistry, Pharmaceutical↗
PubMed1983

Determination of azobenzene and hydrazobenzene in phenylbutazone and sulfinpyrazone products by high-performance liquid chromatography.

A high-performance liquid chromatographic method has been developed for the simultaneous determination of azobenzene and hydrazobenzene in phenylbutazone and sulfinpyrazone raw materials and formulations. The drug raw material or formulation is shaken with 1N NaOH and n-hexane and centrifuged. The n-hexane layer is injected into a chromatograph equipped with a 10-micron cyano-amino bonded phase column. Azobenzene and hydrazobenzene are detected at 313 and 254 nm, respectively; the sensitivities are approximately 1 and 2 ppm, respectively, in the raw materials and formulations.

Azo Compounds↗
PubMed1982

Drug quality assessment methods. I. Gas-liquid chromatographic assay and identification of seven barbiturates.

A gas-liquid chromatographic (GLC) procedure has been developed for the assay and identification of amobarbital, butabarbital, heptabarbital, mephobarbital, pentobarbital, phenobarbital, and secobarbital in single component capsule, elixir, injectable, suppository, and tablet formulations. After extraction into chloroform from an acidified aqueous mixture of the product, the drug is eluted isothermally from a methylphenylsilicone GLC column at 210 or 240 degrees C and quantitated relative to thiamylal internal standard. Results were in good agreement with those obtained using pharmacopeial assay methods. The method is suitable for the rapid assessment of commercial formulations.

Barbiturates↗
PubMed1981

Routine quality evaluation of benzodiazepine drugs to USP-NF specifications.

A GLC procedure was developed for the evaluation of diazepam, chlordiazepoxide, and flurazepam formulations to USP-NF specifications for drug content, content uniformity, impurities, and identity by retention times and peak areas. The polyimide column, instrument zone temperatures, gas flows, internal standard solution, extraction solvent, and auxiliary equipment were the same for each drug. No derivatization of the samples was required. The GLC assay values (mean of 10 individual dosage units) for diazepam and flurazepam products were in good agreement with the results obtained by the pharmacopeial composite assays. With chlordiazepoxide capsules, when the levels of the two pharmacopeial impurities determined by GLC were added to the GLC assay results (mean of 10), athe aggregate values were consistent wit the drug content results found by the nonspecific USP method. The procedure can be made sensitive to impurity levels of approximately 0.01% for 2-amino-5-chlorobenzophenone and to approximately 0.2% for 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide. With the equipment used, the estimated potential outputs in lots per working day for a complete quality profile (drug content, content uniformity, purity, and identity) were seven for chlordiazepoxide if no impurity test was required, five if such a test was required, eight for diazepam, and seven for flurazepam.

Anti-Anxiety Agents↗
PubMed1980

Impurities in drugs IV: Indomethacin.

One lot of indomethacin raw material, five lots of capsule preparations, and three lots of supporitory formulations were screened for impurities by TLC. Only the suppository products exhibited impurities above trace levels. The two main impurities were present at levels estimated at approximately 0.5 and 2%. After isolation from preparative TLC plates, they were identified by NMR, IR, and mass spectroscopy as the alpha-substituted monoglyceryl esters of 4-chlorobenzoic acid and indomethacin, respectively.

Capsules↗
PubMed1980

Impurities in drugs V: Meprobamate.

One lot of meprobamate raw material and 28 lots of tablets were examined for impurities by TLC. All lots contained di-(2-methyl-2-propyl-3-carbamoyloxypropyl) carbonate (V) at levels that ranged between 0.1 and 1.0% of the total drug content. Nine lots also contained low levels of a second impurity (approximately 0.1%), and one of these lots contained a third impurity (approximately 0.1%), neither of which was identified. Estimates of the unidentified impurities were based on the assumption of a TLC response with furfural-hydrochloric acid spray equivalent to that of meprobamate. Compound V was identified by mass spectrometry and PMR and IR spectroscopy and by comparison of the TLC Rf value to that of a synthesized sample of V.

Chromatography, Thin Layer↗
PubMed1978

Simple GLC analysis of anticonvulsant drugs in commercial dosage forms.

A simple, specific GLC procedure is described for the analysis of one sedative and six anticonvulsant drugs in pharmaceutical dosage forms. Sample aliquots of ethotoin, glutethimide, mephenytoin, methsuximide, and phensuximide were shaken with or extracted into ethyl acetate, diluted with the internal standard (diphenyl phthalate) solution, injected into a gas chromatograph, and eluted from a methylsilicon column. Primidone and phenytoin samples (extracted as the free acid) required derivatization with N,O-bis(trimethylsilyl)acetamide prior to chromatography. The same temperature programming conditions and flow rate settings were used for all seven drugs. The GLC results agreed well with those obtained using the pharmacopeial methods.

Anticonvulsants↗
PubMed1977

Selective GLC determination of epinephrine, isoproterenol, and phenylephrine in pharmaceutical dosage forms.

A simple, specific GLC analytical procedure for the quantitation of epinephrine, isoproterenol, and phenylephrine in commercial tablets, powders, inhalation solutions, ophthalmic and nasal drops, and injectable preparations is presented. Samples are taken to dryness where required, the dried residue is reacted with an appropriate trimethylsilylating reagent, and the derivatives are eluted from a methyl silicone column using temperature programming. Quantitation of the flame-ionization detector signal is achieved relative to the dibenzyl succinate internal standard by an electric integrator. The results obtained by applying the method to the analysis of each of the three drugs in several simulated decomposed mixtures were in good agreement with theoretical values, even at impurity levels of up to 80% by weight. When applied to commercial formulations, the procedure was feasible for tablets, powders, and solutions at drug concentrations of 0.2% or greater. The commonly incorporated buffering and antioxidant excipients did not interfere.

Chemical Phenomena↗
PubMed1976

The Shiers arthroplasty of the knee.

Thirty-one patients with rheumatoid arthritis were reviewed after Shiers arthroplasty of the knee joint for which the main indication was intractable pain. Seven patients had the operation done to both knees. This review was done to assess the long-term results two to seven years later. All patients were clinically and radiologically assessed, and our results showed that pain and instability recurred within eighteen months. Thus it is likely that a prosthesis which allows rotation, and in which the bearing surfaces are metal on plastic, will replace the Shiers prosthesis.

Arthritis, Rheumatoid↗
PubMed1975

Specific quantitative gas-liquid chromatographic analysis of methyldopa and some foreign related amino acids in raw material and commercial tablets.

A relatively simple gas-liquid chromatographic (GLC) procedure has been designed for the rapid detection and accurate quantitation of some theoretically possible foreign related amino acid contaminants in alpha-methyldopa raw material and commercial tablets. After trimethylsilylation of the drug or drug mixture with N,O-bis(trimethylsilyl)acetamide in acetonitrile at ambient temperature for 90 min, the derivatives are eluted from a methylsilicone column isothermally at 170 degrees. Quantitation of the components is effected by simple computation relative to dibenzyl succinate as the internal standard. The results obtained by applying the GLC procedure to the analysis of a number of multicomponent synthetic mixtures are in good agreement with the theoretical values. The percentage of label claim values obtained by the GLC method for commercial tablets are compared to those measured colorimetrically by the official U.S.P. procedure. No foreign related amino acid impurities were detected in any of the three commercial dosage forms examined.

Amino Acids↗