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Biomedical subjects

D M Hui

Publications and source records attributed to D M Hui.

4 recordsLinked to original sources

Monitoring of fluorine in urine samples of patients involved in the tokyo sarin disaster, in connection with the detection of other decomposition products of sarin and the by-products generated during sarin synthesis.

We developed a new assay method for fluoride anion (F(-)) a specific metabolite of sarin. Trimethyifluorosilane (TMFS) was derivatized from F(-) with trimethylsilanol, and TMFS was detected with a GC-flame ionization detector (FID) and capillary column system. The linear range, detection limit and recovery rate were 0.02-10 ppm, 0. 01 ppm and 97.3-103.0%, respectively. The patients were reported to be exposed only once to the toxic substance (a bolus exposure). F(-) excretion in urine of the hospitalized patients demonstrated three or four peaks. Other common metabolites of sarin and by-products such as methylphosphonic acid (MPA) and isopropyl alcohol (IPA) also showed two or three peaks. These results suggested that the patients were exposed to not only sarin but also fluoride and isopropyl alcohol containing by-products. The sum of MPA excreted was 0.3-90 mM, far exceeding the human lethal dose of sarin. The residual acetyicholine esterase activity of erythrocytes on admission (4.7-57.2% of the individual reference value) of the patients showed statistically significant relationships only with the initial values of F(-) and the isopropyl methylphosphonate. This evidence also suggested the exposure to fluoride and isopropyl alcohol-containing by-products.

2-Propanol↗

Biological monitoring of metabolites of sarin and its by-products in human urine samples.

More than 20,000 passengers of Tokyo underground trains were intoxicated with warfare toxic chemicals. Most of the patients examined had marked miosis and decreased serum cholinesterase activity. Transient increase of serum CPK activity after 3 days of the exposure was the another sign. We intensively analyzed the metabolites in the urine of 4 patients. The following analytic results indicated the exposure to sarin as well as contaminated compounds such as diisopropyl methylphosphonate (DIMP), ethyl methylphosphonate fluoridate (EMPF, or ethylsarin), diethyl methylphosphonate (DEMP), and ethyl isopropyl methylphosphonate (EIMP). (1) Isopropanol (IPA) and ethanol (EtOH) were detected of large quantities in the urine samples, and were thought to be derived from sarin and the sarin counterpart, EMPF, DIMP, DEMP and EIMP. (2) Monoalkyl methylphosphonic acids (isopropyl methylphosphonic acid (IMPA) and ethyl methylphosphonic acid (EMPA) also were excreted in large amounts with taking the similar excretion pattern of IPA and EtOH. (3) The metabolite only derived from sarin and ethylsarin is F anions whose integral output in the urine was less than the equimolar level of the excreted (IMPA + EMPA + IPA + EtOH). (4) Other corroborative findings were low lethality: of more than 5,510 patients treated, 11 were acutely dead. (5) Nine exposed males had higher sister chromatid exchange (SCE) rate (5.00 +/- 1.48/cell) than the control (3.81 +/- 0.697/cell), because dialkyl methylphosphonates seemed to have alkylating activity and producing DNA adducts. The SCE rate also increased after the in vitro exposure of lymphocytes to dialkyl methylphosphonates.

Chemical Warfare Agents↗

Method for the analysis of the methylphosphonic acid metabolites of sarin and its ethanol-substituted analogue in urine as applied to the victims of the Tokyo sarin disaster.

An analysis method for the methylphosphonic acid metabolites of sarin in urine using trimethylsilyl derivatization and flame photometric detection is described in this report. Authentic reference standards of isopropyl methylphosphonic acid (IMPA) and ethyl methylphosphonic acid (EMPA) as well as methylphosphonic acid were employed to estimate the concentration in human urine. A sample pretreatment procedure was developed for urine using a column of cation-loaded ion-exchange resins (Ag+ -, Ba2+ - or H+ -Dowex) and adjusting the pH of the eluate from the column to 3.75-3.85 improved recovery of the target compounds. The eluate was evaporated to dryness under vacuum prior to trimethylsilylation, to remove water and any hydroxy- or amino-carrying volatile substances. The sarin metabolites, because of their low volatility, were concentrated and could be derivatized for analysis. The use of synthesized authentic sarin and ethylsarin metabolites, i.e., IMPA and EMPA, made it possible to establish the necessary sample pretreatment procedures for derivatization and gas chromatography-flame photometric detection (GC-FPD) analysis. The detection limits were 0.025 ppm both for EMPA and [MPA, and 0.625 microM for MPA, respectively. This method can be useful for estimating the exposure level to sarin by assaying the metabolites in urine and it is applicable to a large numbers of samples.

Chemical Warfare Agents↗