Drugs In Body Fluids Research Articles

Comparative use of three electrokinetic capillary methods for the determination of drugs in body fluids: Prospects for rapid determination of intoxications

Three electrokinetic capillary methods, micellar electrokinetic capillary chromatography, capillary zone electrophoresis and capillary isotachophoresis, are shown to be well suited for the rapid screening and confirmation of drugs in serum and urine of patients with medical drug overdoses (intoxications), situations where rapid identification without precise quantification is needed. Patients' samples obtained from the emergency care unit were analysed in an instrument featuring on-column, fast forward-scanning multi-wavelength detection and the data were compared with those obtained by conventional methods. The drugs studied included salicylate, acetaminophen (paracetamol) and antiepileptics. In cases with high drug concentrations, body fluids can be injected directly or may have only to be diluted (urine) or ultrafiltered (serum) prior to analysis, providing results within about 30 min. Thus, electrokinetic capillary methods can be employed for rapid drug screening, provided that instrumentation with a database for peak identification is available.

Strategies for the monitoring of drugs in body fluids by micellar electrokinetic capillary chromatography

Electrokinetic capillary techniques can exploit numerous separation principles, making them flexible and easily applicable to a variety of separation problems. In recent publications, this emerging technology has been shown to be well suited for monitoring drugs and metabolites in body fluids, including serum, saliva and urine. Most attention has been focused on micellar electrokinetic capillary chromatography (MECC) because it permits the separation and determination of drugs with discrimination being largely based on differences in hydrophobicity. An overview of literature data on the MECC of drugs in body fluids and recent data obtained with antiepileptics in serum and saliva, with model mixtures of illicit drugs, and with extracts from urine specimens that tested positively for opiates and cocaine metabolites are presented. Emphasis is focused on buffer selection and simple sample preparation procedures, including direct injection of body fluids, ultrafiltration and solid-phase extraction.

Capillary Electrophoresis: Analysis of Drugs in Body Fluids

Capillary Electrophoresis: Analysis of Drugs in Body Fluids

Application of quantitative EPR

Although the high sensitivity and broad dynamic range of EPR make it an attractive analytical technique for species with unpaired electrons, the precision and accuracy of spin concentration measurements have often been low. The marked improvement in quantitative EPR is a result of improvements in instrumentation and greater attention being given to operating procedures. In 1962 the lower limit for the EPR determination of polycyclic aromatic hydrocarbons was reported to be ca . 3|ig. Using the same method these compounds have now been determined down to nanogram levels. Aromatic nitro compounds present at submicrogram levels can also be quantified by EPR. A free radical assay technique has been applied to the determination of drugs in body fluids; a morphine concentration in urine of 0.5 |ig cm -3 is detectable. Molybdenum has been determined in sea water with a relative precision of 4.7 % at the 11 pg 1 -1 level and a detection limit of 0.46 pg 1 -1 . By using the EPR signal of [FeF 6 ] 3- the total iron content of solutions containing Mn II , Fe II and Fe III has been measured, the analytical range being 10 -6 -10 -2 M with a detection limit of 6 x 10 -7 M. Diamagnetic metal ions can be estimated by EPR with the aid of spin-labelled chelating reagents, e.g. Zn II over the linear range 10 -6 -10 -3 M with a detection limit of 5.5 x 10 -7 M. Nitrite ion can be determined by EPR with a precision of 0.9% at the 0.5p.p.m. level.

Rapid drug screening using toxi-lab® extraction followed by capillary gas chromatography/mass spectroscopy

We report here a method of analyzing drugs in body fluids by gas chromatography/mass spectroscopy (GC/MS) without the necessity for derivatization. Specimens (urine and serum) were extracted one time using Toxi-Lab extraction tubes. The organic extract was evaporated to dryness, taken up in methanol, and injected directly onto a Hewlett-Packard 5995B GC/MS equipped with a 20-m, 5% phenylmethylsilicone capillary column. Most drugs of clinical interest eluted in 1-10 min and were identified by their mass spectra. Amphetamines were readily distinguished from other sympathomimetic amines; cocaine and its principal metabolite ecgonine methyl ester were readily detected without derivatization. We conclude that the combination of Toxi-Lab extraction and capillary GC/MS analysis provided a rapid, versatile, and efficient method for screening and/or confirming the presence of drugs in biological specimens.

Detection and estimation of antimalarial drugs in body fluids — I. Field test for amodiaquine in urine and saliva

Simple and specific tests for the detection of antimalarial drugs are required during clinical studies on the sensitivity of Plasmodium falciparum to these drugs. A specific colour test has been developed for amodiaquine which is sensitive enough to permit the visual detection of the drug, following the oral administration of a single 600 mg dose, for up to 10 days in saliva and up to seven weeks in urine. The test is based on the oxidation of amodiaquine to a yellow-coloured derivative using an aqueous solution of potassium persulphate and disodium hydrogen orthophosphate as oxidant. The colour has also been determined spectrophotometrically at 560 nm to achieve a lower detection limit of 0.5 microg amodiaquine in 10 ml biological fluid.

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.

Inhibition of Semliki Forest virus multiplication by ribavirin: a potential method for the monitoring of antiviral agents in serum

An enzyme immunoassay (EIA) to determine 50% inhibitory concentrations of ribavirin which suppresses Semliki Forest virus (SFV) multiplication in L-cells is described. Inhibition of SFV replication by ribavirin was measured by detection of viral glycoprotein, on the surface of infected L-cell monolayers, with a horseradish peroxidase labeled monoclonal antibody with specificity for the E 2 glycoprotein of SFV. The concentration of ribavirin in culture fluid associated with 50% reduction of control absorbance values was defined as the 50% inhibitory concentration (IC 50). The IC 50 of ribavirin measured with EIA was mainly influenced by the multiplicity of infection (MOI). At MOI values of 3, 6 and 12 reduction of absorbance values was already obvious at 4.5 h of infection. Furthermore reduction of absorbance values correlated with inhibition of virus production as determined by plaque titration of culture fluids. When the EIA was used for the determination of active ribavirin in serum from treated animals the drug was detectable 1 h after intravenous administration of 4 mg of ribavirin to a concentration of 8 μg per ml serum. The results indicate that this simple EIA is suitable for the monitoring of active antiviral drugs in body fluids.

Enzyme immunoassays for the detection of microbial antigens in body fluids: an overview

Abstract

Variability in the human drug response

Variations in response to drugs may be pharmacodynamic, implying inter-individual differences in the response of receptors in equal concentrations of drug, or pharmacokinetic, implying that individuals receiving the same dose of drug will have different concentrations of drug in their body fluids. Either type of variation can be inherited or acquired. Variations in receptor sensitivity do occur but few instances, inherited or acquired, have well documented clinical relevance. If the dose response relationship for the drug in question is not steep, or if the therapeutic index is low, drug concentration in the region of the receptor will not be critical and causes of kinetic variation are unlikely to be clinically significant. However, it is the many causes of kinetic variation which are best described. These include effects due to drug formulation and changes in the absorption, distribution, metabolism and excretion of drugs. If a consideration of dynamics suggests that drug concentration will determine therapeutic efficacy, analysis and prediction of variability due to these factors is desirable. Prediction requires an accurate description of the system but commonly used pharmacokinetic models may fail when prediction is a goal. The variables, volume of distribution (V d) and rate constant of elimination (K e) are hybrid in that they arise from the interaction of patient and drug characteristics. Important events including macromolecular binding and altered blood flow may not be represented. More data is required to determine the clinical significance of pharmacodynamic variation but better analytical tools are required to deal with kinetic variation when this is important. Specifically, pharmacokinetic models should represent physiological variables and levels of unbound drug in body fluids should receive greater emphasis.

Bioanalysis of cimetidine by high-performance liquid chromatography

Cimetidi, N′-cyano-N-methyl-N′-[2[[(5-methyl- H-imidazol-4-yl)methyl]- thio]ethyl]guanidine, is a specific histamine H 2-receptor antagonist drug that is widely used in medicine to treat gastric ulcer disease and other pathological hypersecretory states. To study the bioavailability of cimetidine, it was necessary to develop a rapid and reliable high-performance liquid chromatography procedure for quantitating the drug in body fluids. In this new procedure, cimetidine is adsorbed directly from urine or plasma, without prior clean-up, on to a mini-column prepacked with C 18 material (Sep-Pak C 18 cartridge). Acetonitrile is used to elute the drug, and the eluate is analyzed by high-performance reversed-phase liquid chromatography on a Partisil 10 ODS column, with an aqueous phosphate-methanol mixture as the mobile phase and UV detection at 228 nm. This method for analysing cimetidine in body fluids is rapid, accurate and precise and differs from previously reported methods in that it eliminates the need for performing bothersome single or multiple, dual- phase solvent extractions. Moreover, slight modifications in the composition of the mobile phase permit the simultaneous determination of cimetidine metabolises.

Therapeutic drug monitoring: a comprehensive and critical review of analytical methods for anticonvulsive drugs.

In the last 20 years, there has been considerable improvement in the determination of anticonvulsive drugs in body fluids. Gas-liquid chromatography, high-performance liquid chromatography and immunological methods (radio-, enzyme-, fluoro-, and nephelo-immunoassays) have progressively supplanted spectrophotometry and thin-layer chromatography. As the number of publications shows, these methods have included a great variety of procedures. At present, gas-liquid chromatography and enzyme-immunoassays are routinely performed, awaiting a wider spread of liquid chromatography and other immunological techniques. This paper is a comprehensive review of the analytical literature on the determination of phenobarbitone, primidone, phenytoin, carbamazepine, valproic acid, ethosuximide, clonazepam, and some of their metabolites in physiological fluids. Gas-liquid chromatographic methods are more particularly reviewed. In order to facilitate the choice between these procedures, a critical selection of the techniques is given and recommendations are made. Emphasis is laid on technical problems encountered with the assays, as well as the need for a rigorous analytical assessment and internal and external quality controls. This review is completed by considerations on the determination of the free drug fraction and on sample collection and storage.

A Review of GC/MS Assays for Abused Drugs in Body Fluids

Abstract GC/MS Assays for Abused Drugs in Body Fluids, a monograph from the National Institute on Drug Abuse (NIDA), deals with the gas chromatographic/mass spectrometric quantitative analysis for eleven commonly abused drugs. Two introductory chapters provide a discussion of the relative usefulness and advantages of chemical ionization GC/MS (CI-MS) versus electron-impact GC/MS and outline principles of operation common to all of the assays.

Determination of Antiepileptic Drugs in Body Fluid by a Competitive Binding Enzyme Immunoassay and Clinical Application

A competitive binding enzyme immunoassay (MARKIT) procedure for determination of the concentration of antiepileptic drugs was assessed and compared with gas-liquid chromatographic (GLC) procedures. Furthermore the Possibility of antiepileptic drugs determination in serum ultrafiltrate and mixed saliva was investigated with MARKIT. The two methods of MARKIT and GLC gave essentially the same results in determination of the serum levels of phenobarbital. The correlation coefficient of MARKIT between GLC was as high as 0.922. The recovery of the phenytoin in serum, serum ultrafiltrate and saliva were 98.1±1.9, 97.5±2.9 and 72.5±3.6%, respectively. The correlation coefficients between serum and serum ultrafiltrate and serum and saliva were 0.926 and 0.654, respectively. These data suggest that MARKIT is a reliable method for the determination of the concentration of antiepileptic drugs in serum, serum ultrafiltrate and saliva.

Gas-chromatographic determination of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU). Part I. Cyclisation to a substituted aminooxazoline

Methods for the gas-chromatographic determination of methyl-CCNU employing cyclisation to the substituted aminooxazoline have been explored. These procedures were found to be unsatisfactory for the determination of the drug in body fluids.

National institute of drug abuse Monograph 32: GC/MS assays for abused drugs in body fluids. US Government Printing Office, Washington, DC, 1980, 202 pp. Single copies free subject to availability

Biomedical Mass SpectrometryVolume 8, Issue 11 p. iii-iii Book Review National institute of drug abuse Monograph 32: GC/MS assays for abused drugs in body fluids. US Government Printing Office, Washington, DC, 1980, 202 pp. Single copies free subject to availability R. L. Foltz, R. L. FoltzSearch for more papers by this authorA. F. Fentiman, A. F. FentimanSearch for more papers by this authorR. B. Foltz, R. B. FoltzSearch for more papers by this authorW. A. Garland, W. A. Garland Hoffmann La Roche Inc., New JerseySearch for more papers by this author R. L. Foltz, R. L. FoltzSearch for more papers by this authorA. F. Fentiman, A. F. FentimanSearch for more papers by this authorR. B. Foltz, R. B. FoltzSearch for more papers by this authorW. A. Garland, W. A. Garland Hoffmann La Roche Inc., New JerseySearch for more papers by this author First published: November 1981 https://doi.org/10.1002/bms.1200081108AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume8, Issue11November 1981Pages iii-iii RelatedInformation

An enzymatic method for microdetermination of aphidicolin: A promising anticancer drug

We have developed a method, based on the in vitro inhibition of purified human DNA polymerase α, the major enzyme of DNA replication, which allows the rapid and accurate determination of pmol amounts of aphidicolin, a promising anticancer drug. The efficacy of this sample method was verified by the determination of aphidicolin in the liver, spleen, blood and urine of mice treated parenterically with the drug. Given its sensitivity and the avoidance of radioactive tracers, this enzymatic method is suitable for the determination of the drug in body fluids and tissue biopsies from living humans. It allows the detection and quantitation of aphidicolin in the presence of inactive metabolite(s) with very similar chemical structure(s) such as those generated by liver microsomal oxidases. The technique will also be useful to monitor the purification of the drug from cultures of Cephalosporium aphidicola.

Gas Chromatographic Methods for the Determination of Antiepileptic Drugs

Despite the availability of a variety of methods for determining the concentrations of antiepileptic drugs in body fluids--including thin-layer chromatography, high pressure liquid chromatography, radioimmunoassay, etc.--gas chromatography remains perhaps the routinely used tool for therapeutic drug monitoring in this area. As a result of the need to improve precision and reproducibility, as well as to reduce costs, among other factors, there has been a continuous technical improvement in the technique. And in the last 10 years, more than 100 papers have described gas chromatography for the determination of antiepileptic drugs. Needless to say, only a small percentage of these publications described methods of a significantly new character. In order to facilitate the task, of comparing methods for the purpose of choosing a technique suitable to a specific need, we have reviewed the analytic parameters described in the 114 publications of the last decade. These parameters include the following: (1) drugs determined, (2) internal standard, (3) amount of sample, (4) extraction procedure, (5) preparation of derivatives, (6) sample injection, (7) detection, (8) column support and temperature, and (9) stationary phase. We present these data in a comprehensive tabular form together with a number of comments concerning specific techniques.

Gas Chromatographic Methods for the Determination of Antiepileptic Drugs

Summary: Despite the availability of a variety of methods for determining the concentrations of antiepileptic drugs in body fluids — including thin-layer chromatography, high pressure liquid chromatography, radioimmunoassay, etc. — gas chromatography remains perhaps the routinely used tool for therapeutic drug monitoring in this area. As a result of the need to improve precision and reproducibility, as well as to reduce costs, among other factors, there has been a continuous technical improvement in the technique. And in the last 10 years, more than 100 papers have described gas chromatography for the determination of antiepileptic drugs. Needless to say, only a small percentage of these publications describes methods of a significantly new character. In order to facilitate the task of comparing methods for the purpose of choosing a technique suitable to a specific need, we have reviewed the analytic parameters described in the 114 publications of the last decade. These parameters include the following: (1) drugs determined, (2) internal standard, (3) amount of sample, (4) extraction procedure, (5) preparation of derivatives, (6) sample injection, (7) detection, (8) column support and temperature, and (9) stationary phase. We present these data in a comprehensive tabular form together with a number of comments concerning specific techniques.

Application of Insolubilized Antibody-Enzyme Immunoassay Technique to Determination of Antiepileptic Drugs in Body Fluids

The insolubilized antibody-enzyme immunoassay technique (MARKIT method) was compared to absorptiometry and homogeneous enzyme immunoassay technique (EMIT method) for determining phenytoin, phenobarbital and primidone in plasma. There was good agreement between results of MARKIT method and absorptiometry, and between MARKIT method and EMIT method.MARKIT method was also applied in determination of concentrations of these drugs in plasma water and mixed saliva. MARKIT method is useful for determining low concentrations of antiepileptic drugs in plasma water and mixed saliva.