Stability of an extemporaneously prepared bleomycin–lidocaine–epinephrine intradermal admixture used in dermatology

Abstract

Bleomycin (0.75 g/L)-lidocaine (3.5 g/L)-epinephrine (3.5 mg/L) admixture (BLE) is indicated for keloids treatment. Effect of short-term storage, influence of BLE components and temperature on efficacy and chemical compatibility of bleomycin were studied. The stability study of BLE was conducted in polypropylene infusion bags at 4℃ and 22℃ over a period of 7 days versus bleomycin diluted alone in normal saline and stored in the same conditions. Active Bleomycin fractions, bleomycin A2 (BA2) and bleomycin B2 (BB2) and inactive demethylbleomycin A2 (DBA2) were analyzed by a validated stability-indicating HPLC method. BA2 and BB2 remained stable for up to 7 days, in both types of bleomycin preparations, whatever the temperature (<10% loss of the initial peak response). In BLE, DBA2 fraction (2.2% at T0) decreased with time. Less degradation was noted with refrigeration (remained % at day 7: 0.86 ± 0.06% at 4℃ versus 0.43 ± 0.02% at 22℃; p = 0.0004). A degradation product (DP) was observed. More significant percentage (of the total of bleomycin fractions) was reached at room temperature (at day 7, 0.97 ± 0.03% at 4℃ versus 1.41 ± 0.06% at 22℃, p = 0.0004). DP attained an identification threshold of 0.5% between the third and fourth days at 4℃ and between the first and the second days at 22℃. A maximum of three days storage at 4℃ and only one day at 22℃ was approved for BLE.