Robert I. Ellin

An apparatus for the detected and quantitation of volatile human effluents

Abstract Methods for the collection and identification of trace amounts of human effluents are presented. A variety of organic structures are included among the effluents: alcohols; ketones; ethers; esters; unsaturated, branched, cyclic and aromatic hydrocarbons; sulfhydryl, cyano and heterocyclic compounds. Over 135 effluents were identified in 16 man tests; tree times this number was observed. Samples were trapped by a cryogenic process in the first eight tests; in the others, porous polymer collection was used. Five compounds found in the effluvia of most test subjects were quantitated. Their respective rates of emission are presented.

Method for isolation and determination of pyridostigmine and metabolites in urine and blood

A procedure is presented for the unique isolation and determination by liquid chromatography of pyridostigmine and its metabolites in urine and blood. Isolation is accomplished by an extension of paired-ion theory using a reversed-phase chromatographic column. The assay of pyridostigmine is linear in concentrations from 40 to 5000 ng/ml. Separation and quantitation of pyridostigmine and metabolites in urine and blood are rapid. An analysis can be performed in 15 min. The method has been applied to the determination of urinary excretion and plasma levels of pyridostigmine administered intramuscularly in rats and to the isolation of acetylcholine, neostigmine, and edrophonium from aqueous solutions.

The stability of sarin and soman in dilute aqueous solutions and the catalytic effect of acetate ion

The hydrolysis of aqueous solutions of organophosphonate compounds such as sarin and soman is a critical factor in biochemical and therapeutic studies. The ability to dilute and transport these compounds with assurance of their purity is imperative to the integrity of such studies. An enzymic method has been used to measure low levels of organophosphonates. Maximum stability data were determined in aqueous and isotonic saline solutions. Acetate ion was found to significantly accelerate hydrolysis.1

Carbamoylated Enzyme Reversal as a Means of Predicting Pyridostigmine Protection Against Soman

The inhibition of human and mammalian red blood cell (RBC) Cholinesterase (AChE) in whole blood in the presence of added pyridostigmine has been examined. After the addition of pyridostigmine to animal and human blood, red cells were separated from plasma at varying intervals and their enzyme activity measured. An apparent rate constant (ke) was derived for the reaction sequence in which carbamate is released from AChE inhibited by pyridostigmine. The constant is a complex of the rates of decarbamoylation and reinhibition of AChE in the blood sample. Rate constants were also determined for the spontaneous reactivation (ks) of carbamoylated AChE in the species studied. Values of ks were greater than ke in corresponding species but varied little between species. Pretreatment of animals with pyridostigmine is known to be an effective therapy against organophosphorus compounds, including soman. The ranking of ke values in mammalian blood was the same as that for the protection against soman in animals: monkey>guinea‐pig>rabbit>rat (ke = 0·15, 0·07, 0·05, 0·02 h−1, respectively). Since ke for human blood (0·20 h−1) was greater than that of monkey, pyridostigmine pretreatment would be expected to be an effective prophylaxis for soman in humans.

Passage of pyridinium oximes into human red cells

Abstract Contrary to popular views, pralidoxime chloride, a positively charged oxime and a drug used to treat poisoning from organophosphorus insecticides, penetrates the red cell membrane. Two other therapeutically related drugs that have similar dissociation constants and chemical function groupings penetrate to negligible extents. Pralidoxime chloride did not bind to either red cell stroma or hemoglobin. The rate of entry into red cells by pralidoxime chloride did not change when the pH of blood was changed by ± 0.6 pH unit. Since the rate of entry of pralidoxime chloride into red cells from plasma was identical to the rate at which oxime passed from red cells into plasma, the process was likely due to simple diffusion. In addition, the fraction of pralidoxime chloride entering the red cells was independent of drug concentration. The penetration was not affected by active transport inhibitors, such as ouabain or N -methyl maleimide. The selective penetration could not be related to lipid solubility.