Isolation of drugs and drug metabolites from biological fluids by use of salt-solvent pairs.

Abstract

Simple rapid procedures based on salt-solvent pairs have been developed for the isolation of drugs and drug metabolites from urine, plasma, and breast milk. The best overall recovery of drugs (84-104%) was obtained by using ammonium carbonate-ethyl acetate extraction. Internal standards were added to the biological samples before the isolation procedure was begun; standards labeled with stable isotopes were preferred. The isolated drugs were quantitated by selective ion detection, with use of an LKB 9000-PDP 12 in electron impact mode, a Finnigan 1015-PDP 8/1 in chemical ionization mode, and an atmo-spheric pressure ionization mass spectrometer. Sen-sitivity of detection was in the nanogram to picogram range. Additional Keyphrases: toxicology #{149}assay of drugs in plasma, urine, breast milk #{149}gas chromatography-mass spectrometry-computer system #{149}drug “profile” At the present time the number of individuals in-gesting drugs on a chronic basis can be counted in the millions. Medically prescribed drugs include oral contraceptives, anticonvulsants, tranquilizers, hypo-glycemic agents, and digitalis preparations. To ensure optimal care, drug concentrations should be moni-tored for many of these patients. If drug monitoring is to be introduced as a routine procedure into the clini-cal chemistry laboratory, simple, rapid procedures that can be applied to a large number of drugs in com-mon use must be developed. In addition, the proce-dures should be capable of identifying several drugs in a single analysis and also amenable to automation. With these requirements in mind, procedures have been developed in our laboratory that provide drug profiles of plasma, urine, and breast milk. Quantifi-