title: Reverse phase high-performance liquid chromatography method for the analysis of amprenavir, efavirenz, indinavir, lopinavir, nelfinavir and its active metabolite (M8), ritonavir, and saquinavir in heparinized human plasma.
abstract: The increasing interest in applying therapeutic drug monitoring (TDM) to antiretroviral therapy is related to the observed interindividual variation in antiretroviral pharmacokinetics that results in a wide range of drug exposure from fixed-dosing regimens and the rapid evolution in the availability of phenotypic assays that generate a target 50% inhibitory concentration (e.g., IC(50)) as a basis for adjusting individual antiretroviral dosages. To facilitate the application of TDM, a method for the simultaneous determination of eight species has been developed. This method is used to quantitate efavirenz and the following protease inhibitors: amprenavir, indinavir, lopinavir, nelfinavir and its active metabolite (M8), ritonavir, and saquinavir. The method using reversed-phase high-performance liquid chromatography (RP-HPLC) was validated. Detection is effected using a photodiode-array detector (PDA) scanning at four different wavelengths. This method allows for detection of all analytes to a lower limit of quantitation of 0.1 to 0.2 microg/mL with an interday variation in CV ranging from 3.5% to 10.4%. The method is being applied to a TDM program that is currently being implemented in the authors' laboratory.
authors.affiliation: Department of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York 14260, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Keil
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Frerichs
authors.forename: Robin
authors.initials: R
authors.lastname: DiFrancesco
authors.forename: Gene
authors.initials: G
authors.lastname: Morse
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000097:blood*; D048588:Benzoxazines; D002219:Carbamates; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003521:Cyclopropanes; D005663:Furans; D017320:HIV Protease Inhibitors / Q000097:blood*; D006493:Heparin / Q000032:analysis / Q000737:chemistry; D006801:Humans; D019469:Indinavir / Q000097:blood; D061466:Lopinavir; D019888:Nelfinavir / Q000097:blood / Q000378:metabolism; D010078:Oxazines / Q000097:blood; D011744:Pyrimidinones / Q000097:blood; D019438:Ritonavir / Q000097:blood; D019258:Saquinavir / Q000097:blood; D013449:Sulfonamides / Q000097:blood
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D002219:Carbamates; D003521:Cyclopropanes; D005663:Furans; D017320:HIV Protease Inhibitors; D010078:Oxazines; D011744:Pyrimidinones; D013449:Sulfonamides; D061466:Lopinavir; C095108:amprenavir; D019469:Indinavir; D006493:Heparin; D019888:Nelfinavir; C098320:efavirenz; D019258:Saquinavir; D019438:Ritonavir