Background

. Intravitreal administration of topotecan shows activity against tumor vitreous seeding in the conservative treatment of retinoblastoma, a malignant tumor originated in the retina of small children. Adequate storage of the intravitreal topotecan solution would allow immediate availability for patients at health care institutions. The goal of the work was to address the stability of the intravitreal topotecan formulation upon reconstitution.

Materials and methods

. Intravitreal topotecan solutions were reconstituted (at a concentration of 0.2 mg topotecan in 1 mL saline solution vehicle, aliquoted in 1 mL plastic syringes) and stored either frozen or at room temperature for different times. Topotecan content was analyzed at time zero and at different conditions using a high performance liquid chromatography method to quantify topotecan lactone (active) and to detect its pH-dependent hydrolysis product, the open carboxylate.

Results

. We found that intravitreal topotecan syringes remained stable at room temperature at least for 24 h, at least for 167 days upon stored frozen at −20°C, and up to 8 h after thawing at day 6. The degradation carboxylate product did not appear in the analyzed thawed samples during the whole study.

Conclusions

. This study confirms the stability of frozen intravitreal topotecan syringes and will help optimize the use of this chemotherapy modality at institutions with low resources. Storage of aliquots will also help reduce personnel exposure to chemotherapy at hospital pharmacies.

中文翻译：

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优化眼科肿瘤药物的存储：玻璃体注射用拓扑替康溶液的稳定性。

背景

。玻璃体腔内给予拓扑替康显示在视网膜母细胞瘤的保守治疗中具有抗玻璃体播种的活性，所述视网膜母细胞瘤是起源于儿童视网膜的恶性肿瘤。玻璃体内拓扑替康溶液的充分储存将使医疗机构的患者可以立即获得药物。该工作的目的是解决重组后玻璃体内拓扑替康制剂的稳定性。

材料和方法

。重构玻璃体内拓扑替康溶液（在1 mL盐溶液媒介物中浓度为0.2 mg拓扑替康，在1 mL塑料注射器中等分），冷冻或在室温下保存不同的时间。使用高效液相色谱法在零时和不同条件下分析托泊替康的含量，以量化托泊替康内酯（活性成分）并检测其pH依赖性水解产物开放羧酸盐。

结果

。我们发现玻璃体内拓扑替康注射器在室温下至少保持24小时稳定，在-20°C下冷冻保存至少167天，在第6天解冻后最多保持8小时。在整个研究过程中分析的融化样品。

结论

。这项研究证实了冷冻玻璃体内拓扑替康注射器的稳定性，并将有助于在资源匮乏的机构中优化这种化学疗法的使用。等分试样的储存也将有助于减少人员在医院药房接受化学疗法的机会。