High performance liquid chromatographic determination of a new antifungal compound, ADKZ in rat plasma.
A high performance liquid chromatography (HPLC) method was developed and validated for the determination of ADKZ (1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl) -3-[N-methyl-N-(4-iodo-benzyl)amino]-2-propanol) in rat plasma. The compound was extracted from plasma samples by liquid-liquid extraction, and an isomeric compound of ADKZ (1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl)-3-[N-methyl-N -(3-iodo-benzyl)amino]-2-propanol) was used as the internal standard (IS), which were analyzed on a reversed-phase C18 column (5 microm, 200 mm x 4.6 mm i.d.). The extracted plasma samples were eluted with acetonitrile-0.018 M triethylamine solution adjusted to pH 3.2 with phosphoric acid (35:65, v/v). The effluent was monitored by a UV detector at 230 nm. The retention time of ADKZ was 7.1 min and IS 8.2 min. The calibration curves were linear in the concentration range of 0.02-2.00 microg/ml with the correlation coefficients greater than 0.999. The quantification limit of ADKZ in rat plasma was 0.02 microg/ml. Intra- and inter-day precision ranged from 2.6 to 7.9% and 3.1 to 9.6%, respectively. The extraction recovery from plasma was no less than 80%. No endogenous interferences were observed with either ADKZ or IS. The method has been successfully used to support the pre-clinical pharmacokinetic studies of ADKZ in rats.
Wen
J
J
Shanghai Key Laboratory for Pharmaceutical Metabolites Research, School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, PR China.
Fan
G R
GR
Hong
Z Y
ZY
Chai
Y F
YF
Yin
X P
XP
Wu
Y T
YT
Sheng
C Q
CQ
Zhang
W N
WN
D000097:Acetonitriles / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D005021:Ethylamines / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D016014:Linear Models; D015394:Molecular Structure; D010756:Phosphoric Acids / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
C518326:1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl)-3-(N-methyl-N-(4-iodo-benzyl)amino)-2-propanol; D000097:Acetonitriles; D000935:Antifungal Agents; D005021:Ethylamines; D010756:Phosphoric Acids; D014230:Triazoles; C030242:phosphoric acid; C016162:triethylamine; C032159:acetonitrile