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At least 19 recordsLinked to original sources
PubMedDate not supplied

Rapid isolation with Sep-Pak C18 cartridges and wide-bore capillary gas chromatography of bromisovalum.

A simple and rapid method for isolation of bromisovalum with Sep-Pak C18 cartridges from human whole blood, plasma, and urine containing allylisopropylacetylurea as an internal standard, is presented. Detection of the drugs was made by nonpolar wide-bore capillary gas chromatography (GC) with flame ionization. The drug-containing samples, after mixing with water, were directly applied to the cartridges and eluted with chloroform-methanol (9:1). The recoveries of bromisovalum with use of the cartridges were excellent. Bromisovalum and internal standard allylisopropylacetylurea could be satisfactorily separated from each other and from impurities with the wide-bore capillary column. The detection limit for bromisovalum was 2-5 ng in an injected volume.

Bromisovalum↗
PubMed1997

Detection of bromisovalum from the bone marrow of skeletonized human remains: a case report with a comparison between gas chromatography/mass spectrometry (GC/MS) and high-performance liquid chromatography/mass spectrometry (LC/MS).

We report a case of totally skeletonized human remains in which a considerable amount of a hypnotic, bromisovalum (bromovalerylurea), was detected from the bone marrow. The unknown skeletal remains were found in a bush, together with empty vials of bromisovalum and a water bottle. The body was identified as a 46-year-old male, who had died about seven months previously. There was no evidence of trauma. The dried bone marrow of both femurs was separately collected and toxicologically analysed by gas chromatography/mass spectrometry (GC/MS) and a high-performance liquid chromatography/mass spectrometry (LC/MS). Bromisovalum was identified from the femurs. The concentration along with the circumstantial evidence suggested possible contribution of bromisovalum to the fatality. However, a considerable quantitative difference was observed between the left and right femur, showing significant post-mortem interference to toxicological evidence. The result showed that multiple sampling at least would be required for quantitative evaluation of post-mortem toxicological evidence. Moreover, the diagnostic value should also be considered with caution in relation to the load to bone marrow ratio of each drug concentration.

Bone Marrow↗
PubMed1993

Characterization of glutathione conjugation in humans: stereoselectivity in plasma elimination pharmacokinetics and urinary excretion of (R)- and (S)-2-bromoisovalerylurea in healthy volunteers.

Characterization of glutathione conjugation in vivo was performed in 12 healthy male volunteers by use of the racemic drug bromisovalum (bromisoval; 2-bromoisovalerylurea) as a model substrate. To study whether the pharmacokinetics of both bromisovalum enantiomers was related to the glutathione S-transferase class Mu phenotype, six subjects who were class Mu deficient and six subjects who were not class Mu deficient participated. After oral administration of 600 mg racemic bromisovalum, enantioselective measurement of unchanged bromisovalum (plasma and saliva) and the diastereomeric bromisovalum mercapturates (urine) showed a pronounced stereoselectivity in all subjects. The plasma clearance of R-bromisovalum was about 12 times higher than that of S-bromisovalum (9.3 +/- 3.7 and 0.78 +/- 0.38 L/min, respectively), which was in agreement with the higher urinary cumulative excretion for the mercapturate derived from R-bromisovalum: 26% +/- 4% of the dose versus 8% +/- 3% of the dose for the mercapturate derived from S-bromisovalum. Both the bromisovalum pharmacokinetics in general and the stereoselectivity in bromisovalum pharmacokinetics were not different for the subjects who were glutathione S-transferase class Mu deficient and the subjects who were not glutathione transferase class Mu deficient.

Administration, Oral↗
PubMed1993

[A fatal case due to intoxication with seven drugs detected by GC-MS and TDx methods].

A twenty-year-old woman was suspected to ingest large amounts of 4 kinds of over-the-counter analgesic and antipyretic drugs, and was found dead. Drugs and poisons were screened by TOXI-LAB drug detection system in the serum and urine, and analyzed by GC-MS and TDx system in the blood, urine, organ tissues and contents of stomach and small intestine. The concentrations (microgram/g) of bromisovalum, apronalide, ibuprofen, ethenzamide, acetaminophen and caffeine in the heart blood were 36.5, 7.58, 43.1, 16.9, 1.22 and 177, respectively. Salicylic acid concentration in the serum was 82.1 micrograms/ml. The concentrations of bromisovalum and caffeine are high enough to be lethal levels. Neither fatal pathological findings nor traumatic wounds were seen. The overdose of both bromisovalum and caffeine and synergistic, additive or combined effects of other 5 drugs above are considered to be her cause of death.

Acetaminophen↗
PubMed1991

T-cell subsets in drug-induced toxic epidermal necrolysis. Possible pathogenic mechanism induced by CD8-positive T cells.

A patient with bromisovalum-induced toxic epidermal necrolysis showed pronounced delayed hypersensitivity to bromisovalum by patch testing. Biopsy specimens from the cutaneous lesion and the site of the positive patch test reaction were analyzed and compared immunohistologically. The findings were similar: most of the mononuclear cells disposed along the dermoepidermal junction and migrating into the epidermis were CD8-positive lymphocytes, whereas the dermal inflammatory infiltrates were composed predominantly of CD4-positive lymphocytes. This case showed the potential usefulness of patch testing in evaluating cases of toxic epidermal necrolysis. We believe that delayed hypersensitivity plays a crucial role in the development of drug-induced toxic epidermal necrolysis. Furthermore, potential effector cells with phenotypic characteristics of CD8-positive lymphocytes (suppressor/cytotoxic T cells) seem to represent important mediators of the epidermal damage of the cutaneous lesion in our case.

Adult↗
PubMed1996

Use of REMEDi HS in emergency toxicology for a rapid estimate of drug concentrations in urine, serum, and gastric samples.

The REMEDi HS is a broad spectrum drug identification system, designed for emergency toxicology screening and forensic applications. The total analysis time is about 20 min. The current library has 555 drugs and metabolites. The system has a software routine that uses an internal standard (IS) to perform quantitative analysis for target compounds when calibrators are available; further, response factors (RF) are supplied for a rapid estimate of drug concentrations when calibrators are unavailable. In the present study, The concentrations of six drugs (bromisovalum, ephedrine, hydroxyzine, diphenhydramine, ranitidine, and lidocaine) and a metabolite of lidocaine (glycinexylidide) were determined using both methods. The slopes of the regression lines between the rapid estimate method and the IS method were generally within 20% of unity, in agreement with the manufacturer's claim. Semiquantitative estimates based on RF also showed good agreement with results obtained using multipoint calibration. These estimates were sufficient for clinical differentiation of routine and toxic levels. Our study demonstrated that the REMEDi HS is particularly useful for a rapid estimate of drug concentrations in the samples from emergency cases when calibrators are not readily available. Our study also showed that this system can be used for the therapeutic monitoring of ranitidine, bromisovalum, lidocaine, and diphenhydrmine.

Blood↗