Determination of the anti-platelet-activating factor BN-50727 and its metabolites in human plasma by high-performance liquid chromatography-solid-phase extraction.
A sensitive and selective HPLC-solid-phase extraction procedure was developed for the determination of platelet-activating factor antagonist BN-50727 and its metabolites in human plasma. The procedure consisted of an automated solid-phase extraction of the drug and metabolites on disposable propylcarboxylic acid cartridges, followed by on-line chromatographic separation. The method was linear from 3.75 to 2400 ng/ml and the limit of quantitation for BN-50727 in plasma samples was 3.75 ng/ml. The within-run precision of the method, expressed as relative standard deviation, ranged from 2.1 to 8.1%. The accuracy, expressed as relative error, ranged from -3.5 to 4.0%. For the main metabolite, the O-demethylated BN-50727 product, the method was linear from 7.5 to 2400 ng/ml and the limit of quantitation in plasma was 7.5 ng/ml. The within-run precision ranged from 2.1 to 11.0% and the accuracy from -5.3 to 1.1%. This paper describes the validation of the analytical methodology for the determination of BN-50727 in human plasma and also of its metabolites. The method has been used to follow the time course of BN-50727 and its metabolites in human plasma after administration of single and multiple doses.
Pruñonosa
J
J
Pharmacokinetic Department, S.A. Lasa Laboratorios, Sant Felíu de Llobregat, Barcelona, Spain.
Parera
L
L
Peraire
C
C
Pla
F
F
Lavergne
O
O
Obach
R
R
D001381:Azepines / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000097:blood*; D012016:Reference Values; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D058924:Thienopyridines; D014230:Triazoles / Q000097:blood*
D001381:Azepines; D010975:Platelet Aggregation Inhibitors; D058924:Thienopyridines; D014230:Triazoles; C067429:Setipafant