title: Determination of tipranavir in human plasma by reverse phase liquid chromatography with UV detection using photodiode array.
abstract: 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.
authors.affiliation: Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Keil
authors.forename: Robin
authors.initials: R
authors.lastname: Difrancesco
authors.forename: Gene D
authors.initials: GD
authors.lastname: Morse
mesh_terms: D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D004355:Drug Stability; D017320:HIV Protease Inhibitors / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011725:Pyridines / Q000097:blood* / Q000627:therapeutic use; D011753:Pyrones / Q000097:blood* / Q000627:therapeutic use; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet / Q000295:instrumentation / Q000379:methods*; D013449:Sulfonamides; D013696:Temperature; D013997:Time Factors
chemical_list: D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; C107201:tipranavir