Masahiko Ohtsuji

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 manufacturers 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.

Experimental studies on postmortem diffusion of ethanol-d6 using rats

In an investigation of postmortem ethanol diffusion deuterium-labeled ethanol-d6 was instilled by peroral gavage immediately after death by CO into the stomach of rat carcasses which were subsequently kept for 12-72 h at 5 or 30 degrees C. The heart blood, abdominal fluid and several tissues were collected and analyzed by head space gas chromatography-mass spectrometry. Rat carcasses showed no macroscopic changes until at least 72 h at 5 degrees C, and 12 h at 30 degrees C. At 30 degrees C, slight macroscopic change was observed after 24 h, moderate change after 48 h and marked change after 72 h. In the abdomen ethanol-d6 diffused gradually into neighboring organs (hepatic left lobe, left kidney and spleen) at 5 degrees C, with ethanol-d6 reaching a peak concentration of 0.75-2.38 mg/g at 24 h. At 30 degrees C, ethanol-d6 was also detected in neighboring organs and reached a peak concentration of 1.06-2.61 mg/g at 12 h. Thereafter, the ethanol-d6 concentration in the liver, kidney and spleen decreased, with concentrations ranging from 0.30 to 0.61 mg/g at 30 degrees C and 0.05 to 1.47 mg/g at 5 degrees C at 48 h. In the femoral skeletal muscle, ethanol-d6 was not detected until 24 h or more storage at 30 degrees C and never detected at 5 degrees C. In the brain and the organs in the thoracic cavity ethanol-d6 was detected after 12 h or more at 5 or 30 degrees C. Comparison of these results of direct peroral gastric instillation with those when ethanol-d6 was injected into the stomach through a laparotomy incision suggest that the brain and thoracic cavity changes were a result of diffusion from the mouth and esophagus. After 24 h at 30 degrees C, the postmortem ethanol production (0.33-0.85 mg/g) was comparable to those in previous reports. These results indicate that the assessment of ethanol concentration in the heart blood and organs in autopsy cases must be carefully conducted in comparison with the alcohol content of the stomach.

Screening of volatile substances and determination of toluene (a thinner component) in the blood and urine in emergency medical care and autopsy cases by the pulse heating method

Screening of volatile substances was performed by pulse heating gas chromatography - mass spectrometry (GC-MS) using a GS-Q column in 211 emergency medical care and 342 autopsy cases. At least 36 standard substances could be separately detected. Six kinds of volatile substances were screened in a total of 553 cases. Toluene and/or hippuric acid were detected in the blood and/or urine in respectively, 4 emergency medical care and 8 autopsy cases. There were 11 abusers (9 males and 2 females) in these 12 positive cases. The ages of the abusers ranged from 13-26 years. There was no particular pattern to the monthly frequency distribution of identification of thinner (toluene) abuse cases, which occurred throughout the year. It is believed that these data at least partly reflect the present status of thinner/glue abuse in Japan. We conclude that pulse heating GC-MS is useful in the screening and quantitative determination of volatile substances including toluene and other thinner/glue components.