title: High-performance liquid chromatographic determination of pyrazoloacridine, a nitro-9-methoxyacridine anticancer agent, in human plasma.
abstract: Pyrazoloacridine (PZA) is a 9-methoxy substituted acridine with a reducible nitro group. PZA has shown selective solid tumor cytotoxicity with activity against hypoxic cells, non-cycling cells and cells expressing the multidrug resistant phenotype. A high-performance liquid chromatographic (HPLC) assay was developed and validated for the determination of PZA in human plasma to support phase II clinical trials. PZA and ethyl orange, the internal standard, were isolated from human plasma by precipitating plasma proteins with methanol, and centrifuging to pellet the proteins. The resulting supernatant was injected onto a cyanopropyl HPLC column eluted isocratically with a mobile phase consisting of 125 mM ammonium acetate buffer pH 4.75-acetonitrile (76:24, v/v). A single wavelength at 460 nm was used for detection. Relative standard deviations for the assay ranged from 5.0% to 12.2% for four different drug concentrations and the limit of quantitation was 100 ng/ml. During the validation short term stability of the drug in plasma and stability of PZA on repeated freezing and thawing of plasma was evaluated. Overall recovery of PZA was 88%. This simple assay was found suitable for studying the clinical pharmacokinetics of PZA.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0622, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Jayewardene
authors.forename: J E
authors.initials: JE
authors.lastname: Santoro
authors.forename: J G
authors.initials: JG
authors.lastname: Gambertoglio
mesh_terms: D000166:Acridines / Q000008:administration & dosage / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002940:Circadian Rhythm; D004355:Drug Stability; D005615:Freezing; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009994:Osmolar Concentration; D011471:Prostatic Neoplasms / Q000097:blood / Q000378:metabolism; D011720:Pyrazoles / Q000008:administration & dosage / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013696:Temperature; D013997:Time Factors
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D011720:Pyrazoles; C064541:NSC 366140