Determination of tipranavir in human plasma by reverse phase liquid chromatography with UV detection using photodiode array

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 mu g/mL (80 mu M). 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 photo-diode-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 mu g/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.