Effective use of organic solvents to remove drugs from biologic specimens.

While studies on the extraction of drugs by various organic solvents are numerous, very few direct comparisons of all the commonly used extraction solvents have been made. Review of the literature and some specific studies undertaken by the author show that the solvents more frequently used in toxicology are not all alike but vary with respect to type of drug being extracted. Hexane, 1-chlorobutane, dichloromethane, chloroform, isopropyl ether, ethyl ether, ethyl acetate, and 1-butanol all extract nonpolar drugs quite efficiently; drugs which have polar functional groups such as alcohols, phenols, carboxylic acids, imides, amides, esters, and sulfonamides require more polar solvents for their removal from aqueous solution in high yield. Ethyl ether and other ethers, ethyl acetate, and ketones are hydrogen bond acceptor molecules and therefore extract electron donor solutes more readily than chloroform, the most commonly used electron donor solvent. Alcohols such as 1-butanol are excellent general drug extractors but pose other problems such as odor and emulsion formation. Hexane, on the other end of the polarity scale, extracts polar solutes very poorly. Thus, chloroform and ethyl ether are the most versatile solvents, although dichloromethane and 1-chlorobutane are finding more use. Solvent costs and health hazards vary within the group of solvents discussed. 1-Chlorobutane and chloroform are relatively expensive, while ethyl ether, hexanes, and dichloromethane are less expensive. No solvent is 100% safe with respect to fire, explosion, and health hazard. While chloroform has the lowest TLV, a safety limit, some of the other solvents have higher vapor pressures. The most useful solvent for small volume extractions is chloroform or chloroform with a small percentage of an alcohol. Although poor recoveries are obtained for many drugs by the small volume extraction technique, more and more use of this approach is expected in the future.