'Analgesics are the most commonly consumed over-the-counter preparatio
ns in the United States. They are used in the treatment of various pai
n syndromes and other medical conditions. Although analgesics are gene
rally perceived to be safe agents, serious toxicity may occur in the s
etting of acute overdose, chronic abuse, or overuse. The indications f
or therapeutic drug monitoring in patients using these medications app
ropriately is as yet not well defined. The emphasis of this discussion
, therefore, is on recommendations for monitoring in situations where
toxicity is suspected. Preanalytical, analytical, and practice issues
including drug interactions, frequency of monitoring, pertinent ancill
ary tests, reporting, and special patient groups at risk for toxicity
are reviewed. Recent information from a major manufacturer of evacuate
d tubes arguing against the use of gel tubes for blood collection for
drug monitoring is included. Colorimetric/enzymatic/immunoassays for t
he routine/stat monitoring of acetaminophen and salicylate and difluni
sal cross-reactivity with most of the currently used salicylate assays
are presented. Achiral and chiral chromatographic assays and newly in
troduced columns such as restricted access media and/or automated chro
matographic systems are reviewed for the analysis of ibuprofen, naprox
en, and the recently introduced tramadol. Finally, concepts regarding
future directions including drug chirality and chiral analysis are pre
sented.