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Biomedical subjects

R D McDowall

Publications and source records attributed to R D McDowall.

14 recordsLinked to original sources
PubMed1990

Two systems for the automated analysis of drugs in biological fluids using high-performance liquid chromatography.

This paper describes two fully automated assays. One for zaprinast, a cGMP specific phosphodiesterase inhibitor, which uses the Gilson-Advanced Automated Sample Processor combination, and the other for an H+/K+ ATPase inhibitor and its sulphone metabolite, which uses direct injection. Both assays were developed to support pharmacokinetic studies at therapeutic doses in small animals as well as in man. Plasma or serum (20-200 microliters) is placed directly into an autosampler and all subsequent manipulations are performed mechanically.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1990

Method validation in the bioanalytical laboratory.

Bioanalytical methods, based on a variety of physico-chemical and biological techniques such as chromatography, immunoassay and mass spectrometry, must be validated prior to and during use to engender confidence in the results generated. The fundamental criteria for assessing the reliability and overall performance of a bioanalytical method are: the evaluation of drug and analyte stability, selectivity, limits of quantification and detection, accuracy, precision, linearity and recovery. The extent to which a method is validated is dependent on its prospective use, the number of samples to be assayed and the use to which the data are put. Specific analytical techniques may require additional validation such as antibody-binding characteristics, peak purity determination, evaluation of matrix effects or structural confirmation of the analyte. Ideally each assay should be cross-validated with a method utilizing a highly specific detector such as a mass spectrometer. Once in use, the performance of the method should be monitored using quality control standards. If a method is set up in another laboratory, the performance of that assay should be monitored with quality control standards sent from the originating laboratory.

Chemistry, Pharmaceutical↗
PubMed1989

Sample preparation for biomedical analysis.

A review of sample preparation techniques for biomedical analysis is presented. Firstly, sample preparation techniques can be divided into unit operations which can be classified into four groups: release of the analyte from the matrix, removal of endogenous material, liquid handling procedures and the enhancement of selectivity and sensitivity. The concept of unit operations gives an analyst a tool with which to evaluate critically any method for preparing a sample for analysis. Secondly, the major techniques of sample preparation (protein precipitation, liquid-liquid extraction, liquid-solid extraction and high-performance liquid chromatography, HPLC) are discussed and their advantages and disadvantages presented. Thirdly, the rationale for the automation of sample preparation is reviewed; in general liquid-solid extraction and HPLC are the best techniques for automation. The means by which this can be effected (either flexible or dedicated automation) is discussed. Finally, techniques such as supercritical fluid extraction, micellar liquid chromatography, microwave energy and immunoextraction which may be applied to biomedical sample preparation are evaluated briefly.

Chemistry Techniques, Analytical↗
PubMed1989

Analysis of 2-cyano-1-methyl-3-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl phenyl]guanidine in dog plasma by liquid-solid extraction and reversed-phase high-performance liquid chromatography.

A method for the determination of 2-cyano-1-methyl-3-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin- 3- yl)phenyl]guanidine (SK&F94836, 1) in plasma is presented. The method involves liquid-solid extraction of the drug by C18 cassettes, with subsequent elution by an AASP LC module for determination by HPLC with UV detection. The assay is rapid, precise, accurate, and specific. The between-day CV values over the concentration range 50-500 ng/mL are 4% or less; this rises to 8% at 25 ng/mL. The corresponding between-day bias is less than 1% over the same range of concentrations. The limit of quantification is 25 ng/mL and the assay can be used for measuring 1 in samples from preclinical studies following either oral or intravenous administration of the compound.

Administration, Oral↗
PubMed1989

Sample preparation for the HPLC analysis of drugs in biological fluids.

Sample preparation for the analysis of drugs in biological fluids consists of a number of unit operations that are used for (i) release of the drug from a conjugate or biological matrix; (ii) removal of endogenous compounds that could interfere with the assay; and (iii) techniques for liquid handling. The trends in sample preparation that have occurred over the past 10 years in the authors' laboratory are discussed. In general, there has been a move from the traditional liquid-liquid extraction to methods using bonded-silica which permit rapid throughput and efficient extraction. Automation of sample preparation has seen further gains in productivity; however, the present generation of equipment lack the control and communication systems that are essential for the development of the automated integrated laboratory of the future.

Automation↗
PubMed1986

Analysis of 5-(4-acetamidophenyl)pyrazin-2(1H)-one (SK&F 94120) in plasma with an Analytichem automated sample processor liquid chromatography module.

A selective and specific assay for 5-(4-acetamidophenyl)pyrazin-2(1H)-one (SK&F 94120), a novel inotropic agent, has been developed. The method incorporates a liquid-solid extraction step with a C18 Analytichem automated sample processor (AASP) cassette, which consists of ten miniature extraction columns. The cassette is then loaded into the AASP auto injector, ready for automated liquid chromatography with UV detection. The AASP consists of a high-pressure sealing chamber which encapsulates each column. The high-performance liquid chromatographic mobile phase is directed through the chamber, and the analytes are eluted onto the analytical column for subsequent separation and measurement. The assay is sufficiently accurate and precise to determine SK&F 94120 at concentrations as low as 0.5 mg/l. The mean coefficient of variation for the concentration range 0.5-10.0 mg/l was 2% with a bias of +/- 1%. The assay has been used for pharmacokinetic and bioavailability studies in several species, including rat, dog, and cynomolgus monkey.

Animals↗
PubMed1986

Recent advances in pharmaceutical chemistry--review II. Histamine H2-receptor antagonists.

The concept of histamine receptors is outlined and the rationale for the synthesis of H2-antagonists presented. Structure-activity relationships among these compounds are described and aspects of absorption, distribution and elimination discussed with particular reference to cimetidine and ranitidine. Oxmetidine, lupitidine and loxtidine are also considered. Methods for the analysis of these drugs in body fluids are presented followed by a discussion of their toxicology. Volunteer and patient studies are also surveyed.

Animals↗
PubMed1979

The distribution of amylobarbitone, butobarbitone, pentobarbitone and quinalbarbitone and the hydroxylated metabolites in man.

Fluid and tissue specimens collected from 30 subjects at autopsy have been assayed for their content of common sedative barbiturates and the corresponding hydroxylated metabolites by g.l.c. Where one barbiturate had been ingested an inverse relationship between lipid solubility of the drug and the distribution in fluids and tissues was observed. In most cases the liver, and in the remainder the spleen, contained the highest concentrations of barbiturate. Bile concentrations were often in excess of those in the corresponding liver. The metabolites of the four sedative barbiturates were usually present in lower amounts than the parent drugs in the fluids and tissues of most subjects but urine often contained much higher concentrations of metabolites--sometimes exceeding that of the parent drug in the liver. Administration of two or more barbiturates together did not appear to affect the distribution and metabolism of the individual drugs.

Adult↗
PubMedDate not supplied

Analytical methods validation: bioavailability, bioequivalence and pharmacokinetic studies. Conference report.

This is a summary report of the conference on Analytical Methods Validation: Bioavailability, Bioequivalence and Pharmacokinetic Studies. The conference was held from December 3 to 5, 1990 in the Washington, DC area and was sponsored by the American Association of Pharmaceutical Scientists, US Food and Drug Administration, Federation International Pharmaceutique, Health Protection Branch (Canada) and Association of Official Analytical Chemists. The purpose of the report is to represent our assessment of the major agreements and issues discussed at the conference. The report is also intended to provide guiding principles for validation of analytical methods employed in bioavailability, bioequivalence and pharmacokinetic studies in man and animals. The objectives of the conference were: 1. To reach a consensus on what should be required in analytical methods validation and the procedures to establish validation; 2. To determine processes of application of the validation procedures in the bioavailability, bioequivalence and pharmacokinetic studies; 3. To develop a report on analytical methods validation (which may be referred to in developing future formal guidelines). Acceptable standards for documenting and validating analytical methods with regard to processes, parameters or data treatments were discussed because of their importance in assessment of pharmacokinetic, bioavailability and bioequivalence studies. Other topics which were considered essential in the conduct of pharmacokinetic studies or in establishing bioequivalency criteria, including measurement of drug metabolites and stereoselective determinations, were also deliberated.

Biological Availability↗
PubMedDate not supplied

Forensic toxicology of some orphenadrine-related deaths.

Toxicological data for orphenadrine in ten cases of fatal poisoning are presented together with results for a further eight cases in which orphenadrine was present in combination with alcohol or another drug. Collapse and convulsions occur within an hour of ingestion of an overdose and death supervenes soon after. Autopsy blood concentrations of orphenadrine in such acute fatal poisonings range from 5.5-37 mug/ml. The unchanged drug was found in the bile and urine and the concentrations in the liver, lung and kidney, though differing between cases, were of the same order in any one case.

Adolescent↗
PubMedDate not supplied

The human distribution of some barbiturate sedatives in combination with miscellaneous CNS-active drugs.

This paper presents 14 cases in which the distribution of barbiturates and the hydroxylated metabolites in combination with miscellaneous CNS-active drugs was studied. In 7 of these cases the other drug present was methadone, and in the remainder dihydrocodeine, morphine, propoxyphene, amitriptyline, meprobamate, cyclizine and dipipanone, diphenhydramine and methaqualine. Amitriptyline, methadone, cyclizine and dipipanone, methaqualone and diphenhydramine appeared to modify the distribution of amylorbarbitone and quinalbarbitone. Likewise, the barbituates seemed to alter the distribution of amitriptyline, propoxyphene and, in one instance, methadone.

Adult↗