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Background: Literature reports innumerable methods for quantification of paclitaxel in biological matrices. Most of these involve complicated extraction procedures like solid phase extraction, separate procedure for elimination of interference of Cremophor El, advanced and expensive instruments. Objectives:The objective of the present research work is to develop and validate a simple, rapid, sensitive, economic and reproducible reverse phase -high performance liquid chromatography method for the estimation of paclitaxel concentration in human plasma that eliminates negative influence of Cremophor El on recovery of paclitaxel.Methods: Chromatographic separation of paclitaxel was carried out using C18 column (150 × 4.6 mm i.d., 4µm particle size, Waters, Australia) with 60% acetonitrile, 40% of 10mM ammonium acetate buffer solution and 0.1% formic acid as a mobile phase at a flow rate of 1.0mL/min at ambient temperature. Validation was performed as per ICH Q2 guidelines.Results: In this system the retention time was 3min. The detection limit was 5ng/mL and limit of quantification with reproducibility was 15ng/mL. Plasma samples were extracted using single solvent (tertiary -Butyl Methyl Ether) liquid-liquid extraction with a recovery of 96-99%. Robustness of the method was established with variation in flow rate, detection wave length and mobile phase composition. Stability of paclitaxel during the study period was studied and found to be stable. Conclusion:The developed method is easy to perform, quick, reproducible with good recovery without negative influence of Cremophor El and applicable to quantify paclitaxel in regular clinical practice for individualization of the therapies.

Turmeric is one of the most used herbal supplements among cancer patients. It reportedly modulates the function of CYP450 enzymes and drug transporters. This study investigates the effect of turmeric on the pharmacokinetics of paclitaxel in breast cancer patients. This is a prospective longitudinal study with 60 breast cancer patients on treatment with single-agent paclitaxel and turmeric. The patients were followed up for two consecutive chemotherapy cycles, and their blood samples were collected, first without turmeric (first cycle) and the next after a 21-day concomitant administration of 2 g/day turmeric (second cycle). Plasma samples were quantified for paclitaxel concentration using High Performance Liquid Chromatograph with UV detector (HPLC-UV) method. The sparse concentration-time data of paclitaxel were subjected to population pharmacokinetic modeling, and then noncompartmental analysis (NCA) was performed on the simulated data to estimate the pharmacokinetic parameters of paclitaxel, before and after turmeric supplementation, for comparisons.The population pharmacokinetic parameters of paclitaxel differed from before to after turmeric supplementation. NCA of simulated concentration-time profiles showed a statistically significant reduction of 7.7% and 12.1% in AUC inf and Cmax, respectively. Given the small magnitude of the changes in pharmacokinetic parameters, the observed changes are not clinically relevant. Thereby, turmeric at the recommended dose can be combined safely with paclitaxel.

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