Spectrophotometric Determination of Anthracycline Anticancer Agents with Aluminum(III) and Chromazurol S in a Nonionic Surfactant Micellar Medium

Abstract

Anthracycline anticancer agents, such as Daunorubicin hydrochloride (DAU), are widely used in acute lymphocytic leukemia and various carcinomata cases. These drugs are DNA intercalations; they interact with topoisomerase II and have an inhibitory effect on nucleic acid synthesis. Although these compounds are cardio-toxic (formation of free radicals), some of them exhibit very good anticancer activities. Therefore, it is very important to monitor the plasma or urine concentration level of anthracycline anticancer agents in patients during therapy. Several classical methods have been used for quantitation of the drugs, including measurement of total fluorescence after the liquid extraction, 1,2 thin-layer chromatography with fluorescence detection, 2,3 radioimmunoassay( 3 H), 1,4 spectrophotometry 5 and voltammetry. 6 HPLC with fluorescence, 7-9 laser-induced fluorometry, 10 electrochemical, 11 and MS, 12 detections are used nowadays. However, there is little analysis reported that used visible spectrophotometry. On the other hand, we have already reported on simple and sensitive determination of various organic compounds, by using a metal ion and a dye.13-15 Here, we have studied the color reaction based on a ternary complex system among an anthracycline anticancer agent, a triphenylmethane dye and a metal ion. We investigated a simple and highly sensitive spectrophotometric determination of anthracycline anticancer agents with aluminum(III) as a metal ion and Chromazurol S (CAS) as a dye, in the presence of a nonionic surfactant. The proposed method was then applied to assays of DAU and its related drugs in pharmaceutical preparations. Experimental Apparatus, reagents and solutions Apparatus.A Shimadzu (Model UV-160) recording spectrophotometer with 10 mm quartz cells was used for conventional measurements. The pH measurements were made with a Horiba (Model F-11) pH meter in combination with a calomel glass electrode. Reagents and solutions. Daunorubicin hydrochloride (DAU) and other anthracycline anticancer agents, analytical-grade reagents, were purchased from Sigma Chemical Co., and used without further purification. The stock solutions were freshly prepared every week. The working solutions (5.0 × 10 -5 mol dm -3 ) were made by suitable dilution of these stock solutions, as required.An aluminum(III) solution was prepared by dissolving aluminum plate (99.99% Wako Pure Chemical Co., Ltd.) in 0.1 mol dm -3 hydrochloric acid. A solution (1.0 × 10 -3 mol dm -3 ) of Chromazurol S (CAS) was prepared by dissolving CAS (Wako Pure Chemical Co., Ltd.) in methanol. A solution of polyoxyethylene 20 stearyl ether (Brij 78, Sigma Chemical Co., Ltd.) was prepared in a 1.0% aqueous solution. A buffer solution (pH 6.4) was prepared by mixing 0.4 mol dm -3 acetic acid and 0.4 mol dm -3 sodium acetate solutions. All other reagents and metals were of analytical grade and were used without further purification. Pure water was prepared by purifying deionized water with a Milli-Q-Labo System just before use. Standard procedure of t...