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Biomedical subjects

R Aderjan

Publications and source records attributed to R Aderjan.

At least 55 records · Page 3Linked to original sources
PubMed1979

Investigation of cardiac glycoside levels in human post mortem blood and tissues determined by a special radioimmunoassay procedure.

Even after the introduction of radioimmunological methods the question of a cardiac glycoside causing or contributing to the death of a patient can not be answered satisfactorily. By means of a special radioimmunoassay procedure for digoxin as well as for the structurally related methyl- and acetylderivatives we measured the concentrations in human blood and post mortem tissues. We investigated the glycoside contents in the blood of intravenously digitalised (Novodigal) al) patients before and after death. At autopsy blood specimens were taken from the heart and the femoral vein. We found an increase of the glycoside level up to a highly toxic range (7--15 ng/ml) especially in the heart blood. Thus post mortem blood levels of digoxin and its derivatives are not suitable for a final decision in alleged cases of fatal poisonings. Measuring various concentrations in tussues and body fluids of the above cardiac glycosides mentioned revealed the kidney concentration to be of high value in confirming a digitalis poisoning. This organ and the heart show the highest tissue concentrations. Interpretations of fatal digitalis poisonings should be based on the additional knowlege of these concentrations. Individual cardiac glycosides may be analyzed by a combination of thin layer chromatography and radioimmunoassay.

Cardiac Glycosides↗
PubMed1979

[A fatal monointoxication by flurazepam (Dalmadorm). Problems of the toxicological interpretation (author's transl)].

A death case following a suicidal overdose of flurazepam (Dalmadorm) is reported. The body was found after 3 month near a highway. The course of the intoxication is in question as benzodiazepines are believed to be relatively save drugs. The death might have occured rapidly because of the acute toxic actions of the drug overdose as well as after a protracted course involving additional complications like inflammatory alteration of the myocard or hypothermia during a coma. Flurazepam and its major metabolites were analysed in blood and urine. The toxic levels of flurazepam (0.51 mg/l), N1-desalkylflurazepam (0.14 mg/1) and N1-hydroxyethylflurazepam (9.0 mg/1) in the blood amounted to 20--50 times higher than therapeutic levels, with flurazepam and metabolites being in only slight altered relation to each other. The overdose is considered to have been above 2.4 g (80 tablets). The resorption of the drug was complete. The analytical findings in blood and urine as well as in the GI-tract are in satisfactory agreement. The analytical data of flurazepam and its metabolites are discussed in detail, taking metabolic and pharmacokinetic parameters, autopsy findings and case circumstances into consideration. A final decision about the course of the intoxication is not possible. This case shows however the fatal consequences of a flurazepam overdose although alcohol or other drugs were not involved.

Autopsy↗
PubMed1979

[A screening radioimmunoassay for 1,4-benzodiazepines in human blood, serum, and urine using anti-oxazepam-hemisuccinate-antibodies (author's transl)].

A simple and specific radioimmunoassay (RIA) was developed for the determination of oxazepam and other 1,4-benzodiazepines in human blood serum and urine (e.g., diazepam, desmethyldiazepam, chlorazepate). For serum a 1:10 dilution, for urine a 1:100 dilution is recommended. Blood and hemolyzed samples need prior extraction by Amberlite XAD-2. The antisera were raised by immunizing "White New Zealand"-rabbits with an oxazepam-3-hemisuccinate bovine serum albumin conjugate. Using 0.1 ml serum dilution the sensitivity is 0.01 mg/l per tube. Especially higher concentrations show a tendency toward underestimation. Being not limited to a single 1,4-benzodiazepine derivative, the specificity of the antisera is also suitable for a screening analysis. Compared to thin-layer chromatographic analysis of urine this assay shows improved sensitivity (0.05--0.1 mg/l in 0.1 ml of a 1:100 dilution = 1 microliter of urine). For forensic investigations, an analysis in the sequence of urine-RIA, blood/serum-RIA, blood/serum-"electron-capture"-gas-liquid chromatography (ECD-GLC) seems to be a helpful approach. Blood levels of diazepam and desmethyldiazepam determined by RIA and GLC after extraction are in satisfactory agreement.

Benzodiazepines↗
PubMed1979

[Cardiac glycosides and metabolites--problems of recovery in tissue extracts. Separation of visible substance spots in the nanogram range (author's transl)].

The recovery measurements in rat tissues performed via i.p. injected radioactive digoxin derivates (3H-digoxin, 125J-digoxin derivative) showed that approximately 50% of the total glycoside content will be extracted. Thus, an addition of digoxin standards to drug-free tissues may lead to false negative determinations. By comparison of the radioactivity before and after extraction the following results were obtained: Recovery from tissues 3H-digoxin 50% 125J-digoxin 40% from serum 3H-digoxin 60% added to drug free tissue homogenates 3H-digoxin 85% After i.p. application of 15 mg/kg of beta-methyldigoxin to BD9 (Berlin)-rats the resulting tissue concentrations were extracted by Amberlite XAD-2. beta-Methyldigoxin and its metabolites digoxin and digoxinbisdigitoxide could be separated and distinguished from artifacts by fluorescence detection on HPTLC-plates with a detection limit of 60 ng/spot. Concentration determined by radioimmunoassay are in satisfactory agreement with HPTLC results.

Animals↗
PubMedDate not supplied

Ethyl glucuronide in human hair.

Ethyl glucuronide (EtG) is considered to be a promising candidate marker of alcohol consumption, but exhibits a short window of detection in blood or urine. Keratinized tissues are known to retain foreign substances and to provide a greater retrospective window of detection than body fluids. Therefore, post-mortem hair, skin swabs, and stratum corneum samples were collected from four subjects with a reported history of alcohol misuse and from seven subjects with a report of regular, socially accepted drinking behaviour, and were investigated for EtG. Additionally, certain specimens were collected from three children, who had not yet consumed any alcoholic beverages. EtG was detectable in most of the hair and stratum corneum samples as well as in perspiration stains from alcohol-consuming subjects. The results indicated that EtG might be formed locally in very small and highly variable amounts. The most important finding was that EtG cannot be expected to be generally detectable in keratinized tissues or perspiration stains from alcohol-drinking subjects, whereas a positive result is always associated with recent alcohol consumption.

Alcohol Drinking↗
PubMedDate not supplied

Corrected retention indices in HPLC: their use for the identification of acidic and neutral drugs.

Thirty-seven selected acidic and neutral drugs were analyzed by HPLC with two-step gradient elution and nine different ODS silica columns. The retention index values (RI) for drugs were calculated against a series of alkyl-arylketones and corrected according to the procedure described earlier. The correction procedure decreased the intercolumn variability of the RI values, and the differences between the RI values obtained for the reference column and other columns substantially declined after correction. The mean standard deviation of uncorrected RI values, calculated for all drugs analyzed on 9 columns, amounted to 25 RI units (range 8 to 40). After correction, the mean standard deviation was 15 RI units (range 3 to 26). The method proved to be suitable for the comparison of results obtained with commercially different ODS silica columns.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

The determination of carbon monoxide in blood by means of electrochemical pocket gas meter.

The Comopac electrochemical device for CO determination in the workplace was adapted for CO and COHb determination in blood. The method enables the determination of COHb from 1 to 95% in 0.5 mL of blood in 20 min. Comparison of results obtained with the Comopac, spectrophotometry, and gas chromatography showed comparable accuracy and precision. The specificity of the electrochemical method was better than spectrophotometry and comparable with gas chromatography.

Carbon Monoxide↗
PubMedDate not supplied

Use of corrected retention indices based on 1-nitroalkane and alkyl arylketone scales for HPLC identification of basic drugs.

Sixteen basic drugs were examined by HPLC (gradient elution in acetonitrile/phosphate buffer, pH 3.2, containing 0.05% nonylamine) with six different ODS-silica columns. The retention indices (RI) were calculated with alkyl arylketone and 1-nitroalkane scales and were subjected to correction, which enabled comparison of results from commercially different column packing materials. The correction procedure was successful for the 1-nitroalkane scale. The scale based on alkyl arylketones was of less use for basic drugs, because some of them eluted earlier than the first reference homologue. This made impossible the proper calculation and correction of RI values for drugs such as cocaine, diphenhydramine, doxepin, and promethazine. The correction procedure of RI values calculated against the series of 1-nitroalkanes is recommended as a method of standardization of HPLC data.

Alkanes↗
PubMedDate not supplied

Ethyl glucuronide: an unusual ethanol metabolite in humans. Synthesis, analytical data, and determination in serum and urine.

Ethyl glucuronide (ethyl beta-D-6-glucosiduronic acid), a minor ethanol metabolite in serum or urine, was determined by gas chromatography-mass spectrometry. Prior to this, ethyl glucuronide was synthesized by the reaction of acetobromo-glucosiduronic acid with ethanol. For the determination of ethyl glucuronide, serum samples were precipitated with acetone, and urine specimens were analyzed after evaporation to dryness. The residues were derivatized with acetic anhydride. Capillary gas chromatography was used to find a retention index value of 1920 for the triacetyl derivative. The mass spectrum of the acetylated ethyl glucuronide was recorded. The calibration is linear in the range investigated (0.1-150 mg/L), and the detection limit is 0.1 mg/L. In individual specimens containing between 0.1 and 4 g ethanol per liter serum, ethyl glucuronide could be detected at concentrations between 3 and 14 mg/L and in the corresponding urine specimens at concentrations between 3 and 130 mg/L.

Ethanol↗
PubMedDate not supplied

Morphine and morphine glucuronides in serum of heroin consumers and in heroin-related deaths determined by HPLC with native fluorescence detection.

A simple, rapid, and sensitive high-performance liquid chromatographic method for the simultaneous determination of serum morphine, morphine-6-glucuronide (M6G), and morphine-3-glucuronide (M3G) based on native fluorescence detection is described. For the extraction of drugs and their metabolites, 200 microL serum was applied to 50 mg of a commercially available octylsilan phase. After isocratic separation in two steps (6.5 min) by reversed phase, the compounds were determined at an excitation wavelength of 245 nm and an emission wavelength of 345 nm (the limit of detection was approximately 5 micrograms/L for each compound). The concentrations of morphine, M6G (with respect to its potential analgesic activity), and M3G were investigated in 20 heroin addicts in police custody and in 10 heroin-associated deaths. The ratios between M6G or M3G and the morphine concentrations and between M6G and M3G are related to the morphine concentration and consequently depend on the time elapsed since the last administration of morphine or heroin. Consequently, the M6G values were found to be higher in cases of death than in the living addicts. By considering the M6G/morphine or M3G/morphine ratios, the narcotic effect of heroin as reflected by morphine and its metabolite concentrations in impaired addicts and cases of fatal poisoning can be better assessed than by use of the morphine concentration alone.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Plasma concentrations of heroin and morphine-related metabolites after intranasal and intramuscular administration.

The disposition of heroin and its metabolites was investigated in four healthy male volunteers following intranasal administration of 6 and 12 mg heroin hydrochloride. In addition, two doses of 6 mg heroin hydrochloride were injected intramuscularly for comparison of pharmacokinetic parameters. Serum samples were analyzed for heroin, 6-acetylmorphine, and morphine by solid-phase extraction-gas chromatography-mass spectrometry. The concentration of morphine glucuronides was determined by high-performance liquid chromatography based on the native fluorescence of the conjugates. Major findings were rapidly rising and declining terminal phases for heroin and 6-acetylmorphine and slowly declining phases of morphine and metabolites after both routes of administration. The area under the curve values of morphine-3-glucuronide depended on dose but not on route of administration. The apparent terminal half-lives of morphine-3-glucuronide ranged from 2.2 to 5.2 h for intranasally administered heroin and were 3.0 and 1.7 h for the intramuscularly applied drug. A mean morphine-3-glucuronide-heroin area-under-curve ratio of 93 for the intranasal route as compared with 38 for the intramuscular route demonstrated that circulating amounts of heroin were about half the size after intranasal administration of the same dose.

Administration, Intranasal↗
PubMedDate not supplied

A preliminary study on the distribution of morphine and its glucuronides in the subcompartments of blood.

The distribution of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) in whole blood, plasma, and packed erythrocytes was studied. Parameters investigated were the hematocrit values (10, 42, 44, and 71%) and the water content of the samples. The blood-to-plasma ratio of morphine concentrations was unaffected by variations in hematocrit and water content, whereas the corresponding ratios for M3G and M6G were strongly influenced. Ratios were 0.53 to 0.65 and 0.52 to 0.62 in specimens with average hematocrit values (42 and 44%, respectively), and the ratios were 0.81 or 0.89 (hematocrit 10%) and 0.27 or 0.28 (hematocrit 71%) in blood samples with different hematocrit values. In contrast to the morphine conjugates, morphine was highly bound to or partitioned into red blood cells (beta e = 55.9). Although the present data are limited, they already demonstrate that conclusions drawn from pharmacokinetic studies and transferred to parent drug to metabolite ratios resulting from forensic blood samples may be biased by the particular biological matrix under investigation.

Centrifugation↗