High-performance liquid chromatographic analysis of the anticancer drug oxantrazole in rat whole blood and tissues.
A reversed-phase high-performance liquid chromatographic (HPLC) assay was developed for the antitumor anthrapyrazole analogue, oxantrazole (OX), in rat whole blood and tissues. Blood samples were mixed with equal volumes of a 25% (w/v) aqueous solution of L-ascorbic acid, whereas tissue samples were homogenized with 1.5-3 volumes of an L-ascorbic acid-methanol-water (1:10:1, w/v/v) mixture to prevent oxidative degradation of OX. Samples were then treated with 60% (v/v) perchloric acid (25-30 microliters/ml of stabilized sample) to precipitate proteins, and centrifuged, with the resultant supernatants analyzed on HPLC utilizing a C8 column. The mobile phase for blood and urine samples consisted of 8% (v/v) glacial acetic acid, 13% (v/v) acetonitrile, 79% (v/v) water, 0.16% (w/v) sodium acetate, and 0.05% (w/v) L-ascorbic acid (final pH 2.7), and was pumped at 1.8 ml/min. Tissue samples were eluted at 2 ml/min with a mobile phase consisting of 8% (v/v) glacial acetic acid, 12% (v/v) acetonitrile, 80% (v/v) water, 0.16% (w/v) sodium acetate, and 0.0;5% (w/v) L-ascorbic acid. OX and internal standard were detected at 514 nm and had retention times of 2.3 and 3.1 min, respectively. The limit of quantitation of OX was 25-50 ng/g. Recovery of OX from biological samples ranged from 50 +/- 0.9% in spleen to 102.8 +/- 1.8% in RG-2 glioma. The analytical method was applied to a pharmacokinetic study in rats.
Hassan
E E
EE
Department of Pharmaceutics, College of Pharmacy, University of Georgia, Athens 30602.
Gallo
J M
JM
D000818:Animals; D000880:Anthraquinones / Q000032:analysis* / Q000097:blood* / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000032:analysis* / Q000097:blood* / Q000493:pharmacokinetics; D001932:Brain Neoplasms / Q000097:blood / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007668:Kidney / Q000737:chemistry*; D008099:Liver / Q000737:chemistry*; D008297:Male; D011720:Pyrazoles / Q000032:analysis* / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000737:chemistry*
D000880:Anthraquinones; D000970:Antineoplastic Agents; D011720:Pyrazoles; C046659:piroxantrone