Determination of DMP 728, a IIb/IIIa receptor antagonist, in rat and dog plasma by high-performance liquid chromatography with fluorimetric detection.
A specific and sensitive HPLC assay for the determination of DMP 728 in dog and rat plasma has been developed. The method involves solid-phase extraction of DMP 728 and the internal standard from plasma using a C2 column. The extracted compounds are derivatized with benzoin under alkaline conditions. Using a mixture of acetonitrile and 0.1 M potassium phosphate buffer (25:75, v/v, pH 7.4) as mobile phase, the derivatized products are separated on a Regis semipermeable surface C8 column and monitored fluorometrically using 325 nm and 425 nm as excitation and emission wavelengths, respectively. The assay is linear from 2.5 to 1000 ng/ml in dog plasma and from 5 to 1000 ng/ml in rat plasma. The limit of quantitation is 2.5 ng/ml using 0.5 ml of dog plasma and 5 ng/ml using 0.5 ml of rat plasma. The assay has been used in pharmacokinetic studies of DMP 728 in dogs and rats.
DuPont Merck Pharmaceutical Company, Drug Metabolism and Pharmacokinetics Section, Newark, DE 19714.
S T
ST
Wu
H F
HF
Stampfli
C M
CM
Banks
T A
TA
Emm
R P
RP
Kapil
P K
PK
Padovani
W M
WM
Lee
S M
SM
Huang
D000097:Acetonitriles; D000818:Animals; D001573:Benzoin; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D004285:Dogs; D005260:Female; D006863:Hydrogen-Ion Concentration; D006878:Hydroxides; D008698:Mesylates / Q000097:blood* / Q000493:pharmacokinetics; D010456:Peptides, Cyclic / Q000097:blood* / Q000493:pharmacokinetics; D010710:Phosphates; D010975:Platelet Aggregation Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D017680:Potassium Compounds; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013696:Temperature; D013997:Time Factors
D000097:Acetonitriles; D006878:Hydroxides; D008698:Mesylates; D010456:Peptides, Cyclic; D010710:Phosphates; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D017680:Potassium Compounds; C085286:DMP 728; C013216:potassium phosphate; D001573:Benzoin; C029943:potassium hydroxide; C032159:acetonitrile