Development and validation method for estimation paclitaxel in plasma

Abstract

Background : Paclitaxel (PTX) is an anticancer drug used in the treatment of many cancer , alone or in combination with other anti-tumors. It has a narrow therapeutic range, a large inter and intra-individual pharmacokinetic variability and haematological toxicity. The most effective pharmacokinetic parameter seems to be the time during which the plasma concentration is over 0.05 μmol/L.

Aim: To develop and validate a new method for PTX quantitation in plasma using HPLC with UV/visible detection.

Methods: A rapid HPLC-UV method was developed for the determination of PTX level in plasma. All solvents used were HPLC grade.

Results: After liquid-liquid extraction, chromatographic separation was achieved using an RP 18 (250 mm) column. The mobile phase was composed of acetonitrile and 0.1 M potassium dihyrogenophosphate (49/51) (v/v). Clonazepam was used as internal standard. This technique was linear over the range 50 ng/mL to 1500 ng/mL (r= 0.998). The evaluation of precision showed that our method is repeatable with a within-day coefficient of variation (CV) ranging from 6.94 to 18.78 % and reproducible for three studied concentrations low, medium and high with day-to-day CV of 14.92, 10.46 and 11.8% respectively. Under these conditions, each analysis required no longer than 12.81 min.

Conclusion: We have developed and validate a new assay for PTX monitoring using HPLC with UV detection which is sensible, specific, reliable and easy to carry out in clinical use for its therapeutic drug monitoring