Effective on-line extraction of drugs from plasma using a restricted-access media column in column-switching HPLC equipped with a dilution system: application to the simultaneous determination of ER-118585 and its metabolites in canine plasma.
The present paper describes the on-line extraction of drugs in plasma using a restricted-access media (RAM) column in a column-switching high performance liquid chromatography (HPLC) apparatus that was equipped with an on-line dilution system. The use of a six- to eightfold on-line dilution ratio for plasma samples resulted in almost 100% recovery of both acidic and basic drugs from plasma. It was found that the relationship between the on-line dilution times and drug recovery efficiencies from plasma was explained in terms of the binding constant between the drug and albumin. The applicability of column-switching HPLC with an on-line dilution system and the effectiveness of the extraction procedure were confirmed by a simultaneous determination of the basic compound, ER-118585, and its metabolites in canine plasma.
Yamamoto
Eiichi
E
Analytical Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan. e-yamamoto@hhc.eisai.co.jp
Kato
Takashi
T
Mano
Nariyasu
N
Asakawa
Naoki
N
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D004285:Dogs; D007201:Indicator Dilution Techniques / Q000295:instrumentation*; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000097:blood*; D010793:Phthalazines / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D015203:Reproducibility of Results; D052616:Solid Phase Extraction / Q000379:methods; D013056:Spectrophotometry, Ultraviolet / Q000295:instrumentation; D013141:Spiro Compounds / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*
C494540:4-((3-chloro-4-methoxybenzyl)amino)-1-(2-hydroxy-7-azaspiro(3.5)non-7-yl)-6-phthalazinecarbonitrile monohydrochloride; D004364:Pharmaceutical Preparations; D010793:Phthalazines; D013141:Spiro Compounds