A simple spectrophotometric evaluation method for the hydrophobic anticancer drug paclitaxel

Ken Sugo,Mitsuhiro Ebara

doi:10.7717/peerj-achem.3

Abstract

In this work, we demonstrate a simple spectrophotometry approach to more accurately quantify and measure paclitaxel (PTX) concentrations. PTX cannot be precisely quantified when mixed with an aqueous solvent, and carries the risk of undergoing crystal precipitation. It is likely that PTX undergoes numerous interactions with aqueous solvents and enters a supersaturated state due to its low solubility. Therefore, a quantitative method is required to measure PTX for quality control before clinical use. Although several high-performance liquid chromatography (HPLC) methods have been reported to date, not all medical facilities have a clinical laboratory with such HPLC devices and analysis techniques. Spectroscopy is a simple and convenient method; however, calibration standards are prepared with an organic solvent, such as methanol and acetonitrile, which, when mixed with PTX, can cause solvent effects that lead to inaccurate results. We generated a calibration curve of PTX at various concentrations (40%, 50%, 60%, 70%, 80%, 90% and 100%) of methanol and evaluated the relative error from HPLC results. The optimum methanol concentration for quantification of PTX was 65.8%, which corresponded to the minimum relative error. The detection limit and quantification limit were 0.030 μg/mL and 0.092 μg/mL, respectively. It was possible to predict the PTX concentration even when polyoxyethylene castor oil and anhydrous ethanol were added, as in the commercially available PTX formulation, by diluting 32-fold with saline after mixing. Our findings show that PTX can be more accurately quantified using a calibration curve when prepared in a methanol/water mixture without the need for special devices or techniques.

Highlights

To properly use an anticancer drug in clinical settings, it is necessary to periodically verify its stability after mixing (Badea et al, 2004; Kawashima et al, 2015)
Spectroscopic drug release evaluation can be successfully undertaken if the test specimen can be prepared with a solvent using the same conditions as those used to generate the standard calibration curve (Kesarwani, Tekade & Jain, 2011), our study focuses on the clinical quality control of non-single component PTX formulations
Calibration curve We found that parameters of the PTX calibration curve, including slope and intercept, varied depending on the solvent used (Fig. 2; Table 1)

Summary

Introduction

To properly use an anticancer drug in clinical settings, it is necessary to periodically verify its stability after mixing (Badea et al, 2004; Kawashima et al, 2015). The hydrophobic anticancer drug paclitaxel (PTX), isolated from the bark of Taxus brevifolia, is one of the most important anticancer drugs and is effective against a variety of human cancers, including breast and ovarian cancer (Huizing et al, 1995; Wani et al, 1971). PTX cannot be precisely quantified when mixed with an aqueous solvent such as saline or glucose injection before use, and carries the risk of undergoing crystal precipitation (Kawashima et al, 2015). A quantitative method is required to measure PTX for quality control

Methods

Results

Discussion

Conclusion