A unique analytical method for the determination of the amount of volatile drug retention by animals during inhalation exposure experiments was developed and evaluated. A large-volume collection system was used to collect and store all exhaled air from the animal. The collected air was analyzed by FT-IR spectroscopy with the use of a Nicolet 5SXB spectrometer and a Spectra-Tech Inc. 10-m long-path gas cell. The developed technique was evaluated with the use of bis-(trifluoromethyl) disulfide (TFD) administered to adult sheep. Control experiments confirmed the system's ability to capture 100% of the administered compound. It was observed that the sheep retained an average of 4.4 mg of this compound per kg of body weight during a 10-min exposure period at an air concentration of 5.0 mg per L. After quantitative analysis, compounds exhaled by the animal were concentrated by passing the collected air through a series of dry-ice and liquid-nitrogen-cooled traps. FT-IR analysis of the collected concentrated products indicated that TFD did not undergo chemical decomposition to form trifluoromethyl sulfide during the exposure experiment. The exposure system and the analytical method developed can be used with both large and small animals.
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