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.
Wu
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DuPont Merck Pharmaceutical Company, Drug Metabolism and Pharmacokinetics Section, Newark, DE 19714.
Stampfli
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Banks
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Emm
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Kapil
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Padovani
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Lee
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Huang
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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