Paclitaxel desensitization protocol: stability study

Introduction
Paclitaxel is an anticancer agent known to cause severe allergic reactions. In some cases, continuing this treatment may be essential for the patient. In such situations, a desensitization protocol must be implemented for subsequent administrations to prevent hypersensitivity reactions. This involves administering increasing doses at 1%, 10%, and 100% of the full paclitaxel dose, with multiple infusion rate steps. Current stability data support a shelf life of 28 days at room temperature for concentrations between 0.3 and 1.2 mg/mL. These data apply to the 100% dose but not to the 1% and 10% doses, which correspond to concentrations below 0.2 mg/mL.

The objective of this study was to assess the stability of paclitaxel over 48 hours at concentrations corresponding to the 1% and 10% doses.

Materials and Methods
Dose calculations were based on a body surface area between 1.4 and 2 m² and a dosage of 175 mg/m². Samples were stored at room temperature, unprotected from light, and diluted in 5% dextrose (D5W). Paclitaxel ACCORD 6 mg/mL vials were used, along with 250 mL polyolefin (POF) bags of D5W. Stability was assessed using high-performance liquid chromatography (HPLC) with UV detection at 227 nm. The mobile phase consisted of 80% acetonitrile and 20% water. An isocratic mode was applied with a flow rate of 1 mL/min, using an Uptisphere C18 column (250 × 4.6 mm, 5 µm). The injection volume was 10 µL and total analysis time was 5 minutes. A calibration curve was established from 2 to 22 µg/mL. Twelve samples were analyzed: 3 bags at 2 mg (8 µg/mL), 3 at 4 mg (16 µg/mL), 3 at 20 mg (80 µg/mL), and 3 at 40 mg (160 µg/mL). The 20 mg and 40 mg solutions were diluted 1:10 prior to analysis. Sampling times were: 0.1 h, 3 h, 6 h, 12 h, 24 h, and 48 h. The acceptance criterion was a degradation of less than 5%.

Results
The method was linear within the 2 to 22 µg/mL range. Retention time was 3.5 minutes, with the calibration curve equation y = 0.9384x + 1.1032. The coefficient of determination (R²) was 0.997, with a coefficient of variation of 1.48%. All four concentrations remained within the 95–105% range, with the following results at 48 hours:
• 99.19% at 8 µg/mL
• 101.81% at 16 µg/mL
• 98.67% at 80 µg/mL
• 99.19% at 160 µg/mL

Conclusion
Paclitaxel diluted in 5% dextrose at concentrations between 8 and 160 µg/mL remains stable for 48 hours. These results support improved coordination between treatment preparation and administration during desensitization protocols.

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