Laforgia Mariarita, Amodio Loredana, Colangiulo Santina, Ungaro Valentina, Gatti Letizia, Lucarelli Gianpiero, Leopoldo Marcello, Nardulli Patrizia, Colabufo Nicola A
S.C. Farmacia e U.Ma.C.A. IRCCS Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco, Bari 70124, Italy.
Biofordrug, Spin-Off of Bari University, Via Dante, Triggiano, Bari 70019, Italy.
ACS Omega. 2022 Jul 14;7(29):25239-25243. doi: 10.1021/acsomega.2c02144. eCollection 2022 Jul 26.
Many anticancer drugs are reported to have low physicochemical stability after dilution; therefore, producers impose short times from reconstitution, dilution, and the end of administration. The precariousness of cancer patients' health in real-life experience within cancer hospitals often forces delays in the drug administration with respect to the standard treatment schedule timing, because of acute toxicities or the need to postpone a control analysis before administration. The public health costs for discarded anticancer drugs due to administration interruptions can be avoided, thanks to independent analytical studies, which integrate the producer's data reported in the technical sheet, referring to the real conditions of preparation in a sterile atmosphere under a cabin in a laboratory dedicated to handling cytotoxic drugs in controlled conditions of temperature, pressure, and particulate contamination. Decitabine is apparently an unstable molecule, whose reported stability is only 3 h at 2-8 °C when diluted, while the mother solution must be immediately used or, otherwise, discarded. This study has investigated the physicochemical stability of decitabine both in diluted infusion bags and in sterile water reconstituted syringes at 4 °C for 0, 24, 48, and 72 h. In all performed studies, the stability-indicating method involves, for the first time, the use of liquid chromatography-tandem mass spectrometry analysis. Unexpectedly, both diluted and reconstituted solutions of decitabine are more stable than previously reported data, with a 48 h-long physicochemical stability at 2-8 °C and protected from light.
据报道，许多抗癌药物稀释后的物理化学稳定性较低；因此，生产商规定了复溶、稀释和给药结束后的短时间限制。在癌症医院的实际临床经验中，癌症患者健康状况不稳定，由于急性毒性或给药前需要推迟对照分析，往往导致药物给药相对于标准治疗计划时间延迟。通过独立的分析研究可以避免因给药中断而导致的抗癌药物废弃所产生的公共卫生成本，这些研究整合了技术文件中生产商报告的数据，参考了在专门处理细胞毒性药物的实验室中，在温度、压力和微粒污染受控条件下的无菌环境中实际的配制条件。地西他滨显然是一种不稳定的分子，据报道其稀释后在2-8°C下的稳定性仅为3小时，而母液必须立即使用，否则丢弃。本研究调查了地西他滨在4°C下于稀释的输液袋和无菌水复溶的注射器中分别放置0、24、48和72小时后的物理化学稳定性。在所有进行的研究中，稳定性指示方法首次采用了液相色谱-串联质谱分析。出乎意料的是，地西他滨的稀释溶液和复溶溶液都比先前报道的数据更稳定，在2-8°C下具有48小时的物理化学稳定性且需避光保存。
