Sensitive analytical method for the novel H1-receptor antagonist HSR-609 in human plasma and urine by high-performance liquid chromatography with pre-column fluorescent derivatization.
A simple and sensitive method for quantitation of HSR-609 (I) in human plasma and urine was developed using HPLC with the fluorescence labelling reagent 4-(N,N-dimethylaminosulfonyl)-7-N-piperazino-2,1,3-benzox adi azole (DBD-PZ). Compound I was extracted from human plasma and urine, and derivatized by reaction with DBD-PZ in the presence of Mukaiyama reagent A, an equimolar solution of 2,2'-dipyridyl disulfide (DPDS) and triphenylphosphine (TPP) in acetonitrile. The reaction mixture was cleaned up by liquid liquid extraction following the derivatization. The conjugate was analyzed by ion-pair-HPLC with fluorometric detection. The quantitation limits for I were 0.5 ng/ml in plasma and 5 ng/ml in urine. Using this method, plasma concentration and urinary excretion of I were studied after oral administration of I to human volunteers.
Hasegawa
H
H
Research and Development Division, Hokariku Seivaku Co. Ltd., Fukui, Japan.
Takahara
E
E
Yamada
T
T
Nagata
O
O
D001584:Benzoxepins / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005453:Fluorescence; D006634:Histamine H1 Antagonists / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D006801:Humans; D008297:Male; D010069:Oxadiazoles; D010879:Piperazines; D011725:Pyridines / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013449:Sulfonamides
D001584:Benzoxepins; C104838:HSR 609; D006634:Histamine H1 Antagonists; D010069:Oxadiazoles; D010879:Piperazines; D011725:Pyridines; D013449:Sulfonamides; C076762:4-(N,N-dimethylaminosulphonyl)-7-(1-piperazinyl)-2,1,3-benzoxadiazole