Biomedical subjects

Frank Musshoff

Publications and source records attributed to Frank Musshoff.

29 records · Page 2Linked to original sources

PubMed2003

Brain amino acid abnormalities in liver disease--a postmortem study.

In a postmortem exploratory study, we examined whether specific amino acid abnormalities associated with liver diseases in vivo may also be detected in human brain samples obtained at clinical autopsies. The branched-chain amino acids (BCAA: valine, leucine, isoleucine) were decreased in the group of patients with liver diseases compared with the control group, whereas the aromatic amino acids (AAA: phenylalanine, tyrosine) were increased. However, the ranges overlapped significantly and were not statistically different. The molar ratio BCAA/AAA was determined to be 1.92 in the collection of patients with liver diseases compared with 2.27 in the control group. In patients with liver disease, ornithine concentrations in the brain appeared significantly decreased whereas glutamine was significantly increased. No significant difference was found in the brain concentrations of proline. Amino acid analysis may contribute to the understanding of pathophysiological mechanisms of liver disease, which are discussed, and may supplement the postmortem diagnosis.

Amino Acids, Aromatic↗

PubMed2002

Chromatographic methods for the determination of markers of chronic and acute alcohol consumption.

The development in chromatographic methods for the determination of markers of alcohol consumption is summarized in this review. The markers included in this article are ethanol in body fluids, ethanol congeners, fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), cocaethylene (CE), carbohydrate-deficient transferrin (CDT), phosphatidylethanol (PEth), 5-hydroxytryptophol (5-HTOL), dolichol, ketone bodies, acetaldehyde-protein adducts, and salsolinol (SAL). Some of these markers for alcohol consumption do not only indicate previous ethanol ingestion, but also approximate the amount of intake and the time when ethanol ingestion last occurred. Basic information about the procedures, work-up, and chromatographic conditions are summarized in tables. Also the main metabolic pathways and reaction schemes are demonstrated in figures. Some examples of typical applications are presented. The author points out that in many of the reviewed papers validation data of the procedures as well as specificities and sensitivities were not clearly presented and consequently were not comparable.

Acute Disease↗

PubMed2002

Automated headspace solid-phase dynamic extraction for the determination of amphetamines and synthetic designer drugs in hair samples.

The technique of automated headspace solid-phase dynamic extraction (SPDE) coupled with gas chromatography-mass spectrometry was evaluated for the determination of amphetamines and synthetic designer drugs in hair samples. Headspace SPDE is a novel method for the solventless extraction of organic compounds in aqueous samples. In a so-called inside needle capillary absorption trap a hollow needle with an internal coating of polydimethylsiloxane is used as extraction and preconcentration medium. Sampling is performed on the solution headspace by passing the gas through the device actively by a syringe. Analytes present in the sample are sorbed onto the deposited stationary phase. The syringe needle is placed into the injection port of a GC and rapid heating of the metal needle induces the desorption of analytes. For the determination of amphetamine, methamphetamine, 3,4-methylendioxyamphetamine (MDA), 3,4-methylendioxymethamphetamine, 3,4-methylendioxyethylamphetamine (MDEA), 3,4-methylendioxyphenyl-2-butanamine and N-methyl-1-(3,4-methylendioxyphenyl)-2-butanamine in human hair samples, 10 mg of hair were hydrolysed with sodium hydroxide. After absorption of analytes for an on-coating derivatization procedure the SPDE needle was directly placed into the headspace of a second vial containing N-methyl-bis(trifluoroacetamide). A validation procedure revealed absolute analyte recoveries between 10.2 and 16.7%. Linearity was obtained from 0.1 to 20 ng/mg with coefficients of correlation between 0.992 and 0.999. Intra- and inter-day precision were determined at two different concentrations and resulted in ranges between 1.4 and 4.1% (intra-day) and 4.2-14.6% (inter-day). Limits of detection between 0.03 ng/mg (MDA) and 0.19 ng/mg (MDEA) were achieved. Results indicated that SPDE is a rapid and sensitive method for the analysis of biological samples. Compared to solid-phase microextraction we found a higher extraction rate coupled with a faster automated operation.

Amphetamines↗

PubMed2002

Simple determination of 22 organophosphorous pesticides in human blood using headspace solid-phase microextraction and gas chromatography with mass spectrometric detection.

A simple and rapid procedure for the determination of 22 organophosphorous pesticides (bromophos-ethyl, bromophos-methyl, chlorfenvinphos, chlorpyriphos, demethon-S-methylsulfon, diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, edifenphos, fenitrothion, fenthion, malathion, methidathion, mevinphos, monocrotophos, omethoate, parathion-ethyl, parathion-methyl, phosphamidon, and quinalphos) in human blood using headspace (HS) solid-phase microextraction (SPME) and gas chromatography (GC)-mass spectrometry (MS) is presented. The effects of various sample additions, incubation temperatures, absorption times, desorption times, and depths of fiber insertion into the injection port of the GC are optimized to enhance the sensitivity of the procedure. The recoveries of spiked blood samples are determined between 70% and 95% compared with samples prepared in water, and absolute recoveries are in the range between 0.1% and 19.6%. For quantitation in the single ion monitoring mode, linearity is established over concentration ranges from 0.025 to 5.0 microg/g with excellent coefficients of correlation (0.991-0.998). The detection limits are in the range between 0.01 and 0.3 microg/g. The time for analysis is 44 min per sample including extraction and GC-MS analysis. HS-SPME in combination with GC-MS is an effective method for the determination of organophosphorous pesticides in human blood and shows a great potential for use in rapid on-site analytical work, which is highly demanded in clinical and forensic toxicology.

Calibration↗

PubMed2002

Fully automated determination of amphetamines and synthetic designer drugs in hair samples using headspace solid-phase microextraction and gas chromatography-mass spectrometry.

This study describes a fully automated procedure using alkaline hydrolysis and headspace (HS) solid-phase microextraction (SPME) followed by on-fiber derivatization and gas chromatographic (GC)-mass spectrometric (MS) detection of amphetamine, methamphetamine, methylendioxyamphetamine, methylendioxymethamphetamine, methylendioxyethylamphetamine, methylendioxyphenylbutanamine, and methylmethylendioxyphenylbutanamine in human hair samples. Ten milligrams of hair is washed with deionized water, petroleum ether, and dichloromethane. After the addition of deuterated internal standards the sample is hydrolyzed with sodium hydroxide and directly submitted to HS-SPME. After the absorption of analytes for an on-fiber derivatization procedure the fiber is directly placed into the HS of a second vial containing N-methyl-bis(trifluoroacetamide) before GC-MS analysis. The limits of detection are determined between 0.01 and 0.17 ng/mg. Absolute analyte recoveries are in the range between 0.3% and 7.5%. Linearity is proven over a range from 0.1 to 50 ng/mg with coefficients of correlation from 0.998 to 1. In comparison with conventional methods of hair analysis, this fully automated HS-SPME-GC-MS procedure is substantially faster and easier to perform without using solvents. It uses minimal sample amounts and has the same degree of sensitivity and reproducibility.

Amphetamines↗

PubMed2002

Cyanide fatalities: case studies of four suicides and one homicide.

Deaths due to cyanide poisoning are relatively rare, largely owing to the restricted availability of cyanide. Nevertheless, the authors report five cases of cyanide fatalities occurring within a few months. Cyanide is one of the most rapidly acting poisons known and is still used for suicide and homicide. The discussion focuses on the circumstances, metabolic changes, pathophysiology, blood levels, diagnosis, and management of cyanide poisoning.

Adult↗

PubMedDate not supplied

Fully automated determination of cannabinoids in hair samples using headspace solid-phase microextraction and gas chromatography-mass spectrometry.

This paper describes a fully automated procedure using alkaline hydrolysis and headspace solid-phase microextraction (HS-SPME) followed by on-fiber derivatization and gas chromatographic-mass spectrometric (GC-MS) detection of cannabinoids in human hair samples. Ten milligrams of hair was washed with deionized water, petroleum ether, and dichloromethane. After the addition of deuterated internal standards the sample was hydrolyzed with sodium hydroxide and directly submitted to HS-SPME. After absorption of analytes for an on-fiber derivatization procedure the fiber was directly placed into the headspace of a second vial containing N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) before GC-MS analysis. The limit of detection was 0.05 ng/mg for delta9-tetrahydrocannabinol (THC), 0.08 ng/mg for cannabidiol (CBD), and 0.14 ng/mg for cannabinol (CBN). Absolute recoveries were in the range between 0.3 and 7.5%. Linearity was proved over a range from 0.1 to 20 ng/mg with coefficients of correlation from 0.998 to 0.999. Validation of the whole procedure revealed excellent results. In comparison with conventional methods of hair analysis this automated HS-SPME-GC-MS procedure is substantially faster. It is easy to perform without use of solvents and with minimal sample quantities, but with the same degree of sensitivity and reproducibility. The applicability was demonstrated by the analysis of 25 hair samples from several forensic cases. The following concentration ranges were determined: THC 0.29-2.20 (mean 1.7) ng/mg, CBN 0.55-4.54 (mean 1.2) ng/mg, and CBD 0.53-18.36 (mean 1.3) ng/mg. 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid could not be detected with this method.

Cannabinoids↗

PubMedDate not supplied

Evaluation of immunochemical drug screenings of whole blood samples. A retrospective optimization of cutoff levels after confirmation-analysis on GC-MS and HPLC-DAD.

Four commonly used immunoassay kits were evaluated for their efficiency in screening for drugs of abuse in whole blood. Six groups of illicit drugs (opiates, cannabinoids, amphetamines, cocain and benzoylecgonine, benzodiazepines, and methadone) were determined by using the homogenous assays ADx and CEDIA DAU and compared with the results produced by means of the inhomogenous assays MTP and Pyxis 24. The measured 86 blood samples were taken from authentic routine analyses between February and September, 2000. Chromatographic confirmation analyses were carried out in all cases (positive and negative immunochemical pretesting). The cutoff levels were retrospectively optimized to reduce false-negative results with priority. Furthermore, false-positive pretests were minimized in order to decrease laboratory work under economical aspects. Specificity and sensitivity were determined for each parameter and assay. For the ADx assay, specificities of 54% (cannabinoids) to 97% (cocaine and metabolite) and sensitivities of about 67% (amphetamine class) to 94% (opiates) were found. The CEDIA assay revealed specificities of 77% (methadone) up to 100% (benzodiazepines) and 75-96% sensitivities for amphetamines and opiates. The MTP immunoassay resulted in specificities of 52% (methadone) to 95% (opiates, cocain, and metabolite) and sensitivities of 92% (amphetamines) up to 100% (methadone). The evaluation of the Pyxis 24 resulted in specificities of 70-96% (benzodiazepines and amphetamines) and sensitivities of 75% (amphetamines) up to 100% (cannabinoids and methadone), respectively. In conclusion, the microtiterplate immunoassays revealed higher sensitivities and have proved to be at an advantage detecting the lowest concentrations of drugs. However, especially for clinical applications in emergency cases with acute intoxications, when screening results are urgently required, homogenic assays such as ADx or Cedia provide preferable alternatives with faster and easier handling.

Amphetamines↗

PubMedDate not supplied

Opiate concentrations in hair from subjects in a controlled heroin-maintenance program and from opiate-associated fatalities.

One month before (T-1) and 12 months after (T12) controlled intravenous administration of pharmaceutical heroin-HCl (10-1000 mg/d) in the context of a heroin-maintenance program, concentrations of opiates in head hair were determined (n = 46), using a validated gas chromatography-mass spectrometry method with limits of detection (LOD) between 0.02 and 0.04 ng/mg. In addition, a collective of opiate-associated fatalities was examined (n = 24). The obtained concentrations in the proximal segment (1 cm) of the patients were between 0.04 and 1.16 ng/mg (mean 0.13 ng/mg) for heroin (HER), between 0.02 and 32.41 ng/mg (mean 1.48 ng/mg) for 6-monoacetylmorphine (MAM) and between 0.03 and 11.79 ng/mg (mean 1.19 ng/mg) for morphine (MOR). With the exception of the analyte HER, there was no other statistically significant difference in the concentrations in comparison to the opiate fatalities [HER 1.55-5.20 ng/mg mean 3.38 ng/mg), MAM 0.04-30.01 ng/mg (mean 2.14 ng/mg), and MOR 0.03-11.87 ng/mg (mean 1.15 ng/mg) in the proximal segments]. After controlled HER administration, a correlation between the dose and the total opiate concentration in the hair was found (r = 0.66). These results disagree with the observations of authors who found only limited dose-concentration relationships after heroin abuse in hair. When considering a single analyte, the coefficient of correlation increased in correspondence to the respective plasma half-life (r = 0.42, r = 0.58, and r = 0.69 for HER, MAM, and MOR). The latter findings are in agreement with the report that states that this correlation is influenced by the plasma half-lifes of analytes. Codeine and acetylcodeine (AC) were detected in 50% and 43.5% (T-1) and 13% and 10.9% (T12) of the samples of the HER-maintenance program, as well as in 33.3% and 16.7% in opiate-associated fatalities, respectively. The lack of differences between obtained opiate concentrations in the hair of participants in a controlled heroin maintenance program and of opiate-associated fatalities does not support the hypothesis that an absence of tolerance can be regarded as a potential cause of death. In addition, the lack of AC, which was also observed in the majority of the deaths, questions its applicability as a characteristic marker of the consumption of illicit heroin.

Codeine↗

PubMedDate not supplied

[Postmortem distribution of sertraline and desmethylsertraline in a fatality].

Sertraline (CAS 79617-96-2) is a relatively safe medication for patients suffering from depression. Data reporting the postmortal distribution of sertraline and desmethylsertraline remain rare as well as reports of risks of side effects following ingestion of the drug. In a case of a young woman found dead in her flat sertraline and desmethylsertraline were identified and quantified in body fluids and tissues by gas chromatography/mass spectrometry and high performance liquid chromatography with diode array detection after alkaline extraction. Sertraline and its desmethyl metabolite were found in the peripheral blood in levels of 0.15 mg/l and 0.20 mg/l, concentrations in liver and bile were markedly higher. By exclusion of other reasons for death a lethal sertraline intoxication was decided. Sertraline is suggested to possess a low inherent toxicity, however, a risk of side-effects which may occur in single cases even under moderate dosages should be considered.

Adult↗

PubMedDate not supplied

[Fatal intoxication with amisulpride and presentation of organ distribution].

Amisulpride is a substituted benzamide used as an atypical antipsychotic drug. It antagonizes dopamine D2 and D3 receptor-mediated effects with greater affinity for the limbic system suggesting better neurological tolerance than classical neuroleptics. However, occasionally amisulpride intoxications associated with seizures, comatose conditions and agitation, hyperthermia, tachycardia, prolongation of the QT interval and extrapyramidal features have been described. A 27-year-old female with a medical history of psychosis and amisulpride therapy was found dead at home. By means of high performance liquid chromatography coupled with mass spectrometry (LC/MS) an amisulpride concentration of 13.4 mg/l was found in the peripheral blood. A lower concentration in the brain and an extremely high concentration in bile can be explained by the polarity and hydrophobic character of the substance. After macroscopic and histological exclusion of other causes of death the results of the toxicological analysis were consistent with the assumption of a fatal amisulpride overdose.

Adult↗