ORIGINAL ARTICLE Filiz Arioz Ozdemir Æ Beril Anilanmert Æ Mursit Pekin Spectrophotometric investigation of the chemical compatibility of the anticancer drugs irinotecan-HCl and epirubicin-HCl in the same infusion solution Received: 16 April 2004 / Accepted: 18 November 2004 / Published online: 10 June 2005 Ó Springer-Verlag 2005 Abstract The use of infusional chemotherapy, especially in an ambulatory setting, absolutely requires that the individual agents remain stable in solution at room temperature and that the drugs be compatible. Because of this, investigation of the chemical compatibilities of chemotherapeutic drug combinations given in the same infusion solution is quite important especially if the drugs are to remain in solution for long periods. Thus, the visual and chemical compatibility of irinotecan and epirubicin in the same infusion solution were investi- gated using both reference standards and pharmaceuti- cal dosage forms. No sign of incompatibility was observed upon visual examination by means of effer- vescence, pH change, precipitation and colour change. But a chemical incompatibility was observed using a spectrophotometric method in the spectra of irinotecan- HCl and epirubicin-HCl. The molar ratio of epirubicin- HCl/irinotecan-HCl at which the interaction reached a maximum was found to be 2:1. The chemical interaction occurred immediately after admixing and no visual or spectral change was noticed for 24 h after the interaction had occurred. It is concluded that these drugs are chemically incompatible. While the applicability of these two drugs in combination is investigated in further pharmacological studies, their chemical interaction should also be a consideration. The positive or negative contribution of this interaction to the pharmacological effect of the combination might be of importance, and therefore should be investigated in further clinical trials. Keywords Irinotecan Æ Epirubicin Æ Chemical compatibility Æ Interaction Æ Spectrophotometry Æ Visual compatibility Introduction The use of drugs in combination is widespread in cancer chemotherapy. Combination therapy is usually more toxic than single-agent therapy, but occasionally, com- binations of drugs with different mechanisms of actions and side-effect profile can be as or less toxic than single- agent therapy. So, it is sometimes possible to decrease serious dose-limiting side effects through combined drug therapy. Also combination chemotherapy can decrease the resistance of tumor cells. Technological advances are on the horizon that will provide the capacity to administer multiple drugs through a single access site to allow the use of a single delivery source, thus obviating the need for admixtures of drugs [18]. Because the administration of infusions sometimes needs a long period of time, it would appear that the best and easiest method is to give more than one drug in the same infusion solution. From a practical point of view, the administration of infusional chemo- therapy, especially in an ambulatory setting, absolutely requires that the individual agents remain stable in solution at room temperature and that the drugs be compatible [18] Because of this, investigation of the chemical compatibility of chemotherapeutic drugs given in the same infusion solution, before clinical studies, is quite important. Thus, the visual and chemical com- patibility of the anticancer drugs irinotecan and epiru- bicin in the same infusion solution was investigated. Irinotecan-HCl (I; Fig. 1) is a new drug which has antitumour activity in a wide range of malignancies, such as metastatic colorectal cancer, upper gastrointestinal, pancreatic, lung and breast cancer, and gynaecological malignancies.[2, 5, 9]. Camptothecin derivatives are inhibitors of the enzyme topoisomerase I, which inhibits nucleic acid synthesis by interfering with the coiling and recoiling of DNA during replication. Irinotecan exists in an active lactone form and an inactive hydroxy acid anion form [2]. A closed-ring lactone configuration is necessary for topoisomerase I inhibition. Irinotecan-HCl F. A. Ozdemir (&) Æ B. Anilanmert Æ M. Pekin Department of Analytical Chemistry, Faculty of Pharmacy, Marmara University, Tibbiye Cad., 81010 Haydarpasa, Istanbul, Turkey E-mail: filiz93@yahoo.com Fax: +90-216-3452952 Cancer Chemother Pharmacol (2005) 56: 529–534 DOI 10.1007/s00280-004-0990-z