Walker Scott E, Charbonneau Lauren F, Law Shirley
, MScPhm, is Director of Pharmacy and of the Division of Pharmacology, Sunnybrook Health Sciences Centre, and Associate Professor, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario.
, BSc(Pharm), is Manager of the Odette Cancer Centre Pharmacy, Sunnybrook Health Sciences Centre, Toronto, Ontario.
Can J Hosp Pharm. 2014 Mar;67(2):102-7. doi: 10.4212/cjhp.v67i2.1334.
Solutions of bortezomib 1.0 mg/mL for IV administration are reportedly stable for up to 42 days. Recent publications have reported that the safety profile of bortezomib is better with subcutaneous administration than with IV administration.
To evaluate the stability of higher-concentration bortezomib solutions for subcutaneous administration (i.e., 2.5 mg/mL in 0.9% sodium chloride [normal saline or NS]).
On study day 0, twelve 3.5-mg vials of powdered bortezomib were each reconstituted with 1.4 mL of NS to prepare solutions with concentration 2.5 mg/mL. Half of the solutions were subsequently stored in the original vials and half were transferred to syringes. Three of each type of container were stored in the refrigerator (4°C) and the other 3 of each type were stored at room temperature (23°C). Concentration analysis and physical inspection were completed on study days 0, 1, 2, 8, 12, 14, 19, and 21. The concentration of bortezomib was determined by a validated liquid chromatographic method with ultraviolet detection. The expiry date was determined according to the time to achieve 90% of the initial concentration, based on the fastest degradation rate calculated from the 95% confidence interval of the observed degradation rate.
The analytical method separated degradation products from bortezomib such that the concentration was measured specifically and accurately (with absolute deviations from known concentration averaging 2.99%), with intraday and interday reproducibility averaging 1.51% and 2.51%, respectively. During the study period, all solutions were observed to retain at least 95.26% of the initial concentration in both types of containers at both temperatures.
Bortezomib (3.5 mg in manufacturer's vial) reconstituted with 1.4 mL NS is physically and chemically stable for up to 21 days at 4°C or 23°C when stored in either the manufacturer's original glass vial or a syringe. Subcutaneous injection of bortezomib represents a change in practice, and there is a potential safety concern if a solution of the increased concentration used for subcutaneous administration (2.5 mg/mL) is inadvertently used to prepare a dose intended for IV administration. Therefore, it is recommended that sites switching to subcutaneous administration of bortezomib eliminate 1.0 mg/mL IV solutions altogether or institute substantial barriers to prevent IV administration of the higher concentration of bortezomib.
据报道，用于静脉注射的1.0毫克/毫升硼替佐米溶液在长达42天内是稳定的。最近的出版物报道，硼替佐米皮下给药的安全性优于静脉给药。
评估皮下给药的高浓度硼替佐米溶液（即0.9%氯化钠[生理盐水或NS]中2.5毫克/毫升）的稳定性。
在研究第0天，将12瓶3.5毫克的硼替佐米粉末小瓶分别用1.4毫升生理盐水复溶，以制备浓度为2.5毫克/毫升的溶液。随后，一半溶液储存在原小瓶中，另一半转移到注射器中。每种类型的容器各有3个储存在冰箱（4°C）中，每种类型的另外3个储存在室温（23°C）下。在研究第0、1、2、8、12、14、19和21天完成浓度分析和物理检查。硼替佐米的浓度通过经过验证的带有紫外检测的液相色谱法测定。根据达到初始浓度90%的时间确定有效期，该时间基于从观察到的降解率的95%置信区间计算出的最快降解率。
该分析方法将降解产物与硼替佐米分离，从而能够特异性且准确地测量浓度（与已知浓度的绝对偏差平均为2.99%），日内和日间重现性分别平均为1.51%和2.51%。在研究期间，观察到所有溶液在两种温度下的两种类型容器中均保留至少95.26%的初始浓度。
用1.4毫升生理盐水复溶的硼替佐米（制造商小瓶中3.5毫克），当储存在制造商的原装玻璃瓶或注射器中时，在4°C或23°C下物理和化学稳定性可达21天。硼替佐米皮下注射代表了一种实践中的改变，如果无意中将用于皮下给药的更高浓度溶液（2.5毫克/毫升）用于制备静脉给药剂量，存在潜在的安全问题。因此，建议转向硼替佐米皮下给药的机构完全消除1.0毫克/毫升的静脉溶液，或设置实质性障碍以防止静脉注射更高浓度的硼替佐米。
