Tipranavir has recently received accelerated approval from the FDA. The initial clinical use of tipranavir will be for patients with prior virologic failure with the presence of key HIV-1 protease inhibitor mutations. In Phase III trials patients with greater virologic response also had higher trough tipranavir concentrations (BI product information 2005). In addition, hepatotoxicity was concentration-related with a higher incidence in those patients exceeding a trough plasma concentration of 48.2 microg/mL (80 microM). Therefore, tipranavir may be an HIV-1 protease inhibitor for which therapeutic drug monitoring (TDM) may be helpful in optimizing outcomes. To quantitate tipranavir concentrations in human plasma, a method using reversed phase high performance liquid chromatography (RP-HPLC) was validated. Detection was effected using a photodiode-array detector, scanning at a wavelength of 254 nm. This method allows for detection of tipranavir to a lower limit of quantitation of 0.390 microg/mL with an interday variation in control value ranging from 2.9 to 4.6%. The method is being used in a clinical therapeutic drug monitoring program that is ongoing in our laboratory.