Blood, Volatile amines

A recent study of the Conway method applied to whole blood (R2) stresses the importance of the ammonia derived from the breakdown of blood constituents in the highly alkaline diffusion medium and recommends a correction for this. It is suggested that two diffusions be performed, one for 40 and one for 80 minutes. The difference between the two values would represent the actual preformed ammonia of the blood. This problem has been discussed by others (B6, S3), as well as by Conway (C5). The requirement for a 40-minute diffusion in order to obtain a complete yield of ammonia from the sample is a major handicap of the Conway apparatus. The Seligson method requires only 10 to 20 minutes, resulting in much less time for artifact. The use of the titration of basic (R2) leads to the inclusion of much volatile base which is not ammonia, and much of the apparent formation of ammonia during diffusion is probably volatile amines, for it is not seen so constantly using Nesslerization methods. 

Derivatization is also useful to detect volatile metabolites. Liu et al. [282] described a specific, rapid, and sensitive in situ derivatization solid-phase microextraction (SPME) method for determination of volatile trichloroethylene (TCE) metabolites, trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol (TCOH), in rat blood. The metabolites were derivatized to their ethyl esters with acidic ethanol, extracted by SPME and then analyzed by gas chromatography/negative chemical ionization mass spectrometry (GC-NCI-MS). After validation, the method was successfully applied to investigate the toxicokinetic behavior of TCE metabolites following an oral dose of TCE. Some of the common derivatization reagents include acetyl chloride and TV-methyl-iV- ft-b u (y Idi methyl si I y I) tro (1 uoroacctam i nc (MTBSTFA) for phenols and aliphatic alcohols and amines, dansyl chloride and diazomethane for phenols, dansyl chloride for amines, acidic ethanol and diazomethane for carboxylic acids, and hydrazine for aldehydes. 

Cocaine is a tertiary amine, methamphetamine a secondary amine, and amphetamine a primary amine. Typical pK values for [RjNHjT [RjNHj], and [RNH3] are, respectively, 9.76, 10.66, and 10.63. The salts are water soluble and hence more easily ingested, but they are nonvolatile, so difficult to inhale. The free bases are less water soluble but relatively volatile, hence easier to inhale. Since the lungs are richly supplied with blood vessels, inhalation results in higher and faster bioavailability of the drugs. 

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