High-performance liquid chromatographic determination of a new beta-lactamase inhibitor and its metabolite in combination therapy with piperacillin in biological materials.
[2S-(2 alpha,3 beta,5 alpha)]-3-Methyl-7-oxo-3-(1H-1,2,3-triazol-1-yl- methyl)-4-thia-1-azabicyclo [3.2.0]-heptane-2-carboxylic acid 4,4-dioxide (YTR-830H) is a new beta-lactamase inhibitor and the combination therapy of this compound with piperacillin is now under study. For the determination of the beta-lactamase inhibitor and piperacillin in biological materials, plasma and visceral tissue homogenates were deproteinized, whereas diluted urine and filtered faeces homogenates were treated with a Sep-Pak C18 cartridge. In order to assay the inactive metabolite of beta-lactamase inhibitor, each sample was treated with a Sep-Pak C18 cartridge. Aliquots of each preparation were chromatographed using ion-pair and reversed-phase chromatographic techniques on a high-performance liquid chromatograph equipped with a UV detector, set at 220 nm. The detection limits of beta-lactamase inhibitor and piperacillin were 0.2 microgram/ml in plasma, 2.5-5.0 micrograms/ml in urine and 0.2-0.5 microgram/g in visceral tissue and faeces. Those of the metabolite were 1.0 microgram/ml in plasma, 2.5-5.0 micrograms/ml in urine and 1.0 microgram/g in visceral tissue and faeces. A precise and sensitive assay for the determination of the beta-lactamase inhibitor, its metabolite and piperacillin is described, and their stabilities in several media are reported.
Marunaka
T
T
Biological Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Maniwa
M
M
Matsushima
E
E
Minami
Y
Y
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005243:Feces / Q000032:analysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D010397:Penicillanic Acid / Q000032:analysis* / Q000097:blood / Q000652:urine; D010878:Piperacillin / Q000032:analysis* / Q000097:blood / Q000652:urine; D051381:Rats; D013045:Species Specificity; D013056:Spectrophotometry, Ultraviolet; D000078142:Tazobactam; D014018:Tissue Distribution; D065093:beta-Lactamase Inhibitors
D007202:Indicators and Reagents; D065093:beta-Lactamase Inhibitors; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin