Determination of a HIV protease inhibitor (DMP 450) in animal and human plasma by solid-phase extraction and high-performance liquid chromatography.
Extraction of DMP 450 from plasma was performed with C2 solid-phase extraction columns, using 0.1 M ammonium acetate in 90% methanol to elute DMP 450. The extraction recovery over the range of 10 to 10 000 ng/ml averaged 81.0, 96.2, 77.4, 95.2 and 68.0% from rat, dog, monkey, chimpanzee (25-10 000 ng/ml) and human plasma, respectively. HPLC analysis was carried out with a C18 column and a mobile phase of acetonitrile, methanol and 30 mM potassium phosphate (pH 3), the composition dependent on the type of plasma being analyzed, and monitored at a wavelength of 229 nm. Intra-day and inter-day coefficients of variation were less than 9.9 and 12.9%, respectively. Absolute differences were less than 11.5%.
Grubb
M F
MF
Drug Metabolism and Pharmacokinetics Section, DuPont Merck Pharmaceutical Company, Stine-Haskell Research Center, Newark, DE 19714, USA.
Robinson
C A
CA
White
S J
SJ
Krauthauser
C L
CL
Shum
L
L
D000097:Acetonitriles; D000818:Animals; D001381:Azepines / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D004285:Dogs; D017320:HIV Protease Inhibitors / Q000097:blood*; D000882:Haplorhini; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000432:Methanol; D002679:Pan troglodytes; D010710:Phosphates; D017680:Potassium Compounds; D051381:Rats; D012680:Sensitivity and Specificity; D014508:Urea / Q000031:analogs & derivatives* / Q000097:blood
D000097:Acetonitriles; D001381:Azepines; D017320:HIV Protease Inhibitors; D010710:Phosphates; D017680:Potassium Compounds; D014508:Urea; C013216:potassium phosphate; D000432:Methanol; C099851:DMP 450; C032159:acetonitrile