Quantitative compliance markers and associated methods for monitoring patient compliance with medication prescriptions associated with compliance markers have been found to eliminate the need for specific quantitative relationships for each new drug tested. Such compliance markers and methods for monitoring patient compliance utilize pharmacologically inert substances, namely the weak acids benzodiazepines, or non-metabolizable substances in association with an underlying drug at a measurable dosage, so as to correlate compliance marker concentration with underlying medication concentration to determine amount of actual medication ingested.