Physicochemical stability study of paclitaxel in polyproylene syringes for allergologic use

Paclitaxel, a chemotherapeutic agent from the taxane family, is widely used in the treatment of breast, ovarian, and lung cancers. However, it is known to cause hypersensitivity reactions (HSRs) in about 10% of patients, which can range from mild to severe. These reactions often necessitate allergological testing and may impact the therapeutic regimen. While the management of HSRs is critical, no data is available on the physicochemical stability of paclitaxel at very low concentrations in polypropylene syringes, which are often used in allergological tests.

A stability indicating ultra-performance liquid chromatography coupled to a Photodiode Array Detector (UPLC-DAD) method was developed and validated according to the ICH guidelines. The study aimed to evaluate the stability of paclitaxel at three different concentrations 0.6mg/mL, 0.06mg/mL, and 0.006mg/mL, diluted in sodium chloride 0.9% solution and stored in polypropylene syringes under various conditions: -20°C, 5°C, 25°C, and 40°C. The stability was assessed over 28days using UPLC to measure paclitaxel concentration and observe potential degradation products. The physical stability was also evaluated by monitoring pH, color, and turbidity.

Paclitaxel remained chemically stable for 28days when stored at 5°C and 25°C at all concentrations, with degradation observed at 40°C. At -20°C, both physical and chemical stability was maintained for the full 28-day period. However, physical instability, evidenced by the appearance of precipitates and increased turbidity, was observed at 40°C by day 6 and at 4°C and 25°C by day 21, particularly in the more dilute solutions.

The study highlights that paclitaxel can be pre-prepared and stored at low concentrations in polypropylene syringes for allergological use, particularly under refrigerated conditions, improving hospital workflow efficiency. However, the findings emphasize the necessity of adhering to strict storage guidelines to prevent both chemical and physical degradation, especially at higher temperatures. These results have significant implications for clinical practice, particularly in managing HSRs in oncology settings.