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CriPec® docetaxel leads ideally via more selective tumour targeting to higher intratumoural drug concentrations.This method was developed and validated for determination of CriPec® docetaxel and its released equivalent.This assay was developed to discriminate the pharmacokinetic profile of bound drug in samples in relation to released drug.In order to investigate the pharmacokinetic profile of total and released docetaxel a reliable and robust assay was developed.A sensitive, high-performance liquid chromatographic method was developed and validated, for determination of docetaxel from docetaxel-entrapped core-crosslinked polymeric micelles (CriPec®) in human potassium EDTA plasma and released docetaxel to support the clinical development of Cripec® docetaxel. CriPec® docetaxel is a novel formulation of docetaxel – covalently conjugated via a linker agent in a nanoparticle. The analytical characterization of CriPec® docetaxel comprises determination of both released and total docetaxel, the first being the already deconjugated docetaxel, whereas total is representative of all docetaxel (deconjugated as well as CriPec® nanoparticle conjugated material). Total docetaxel was determined by incubation of human plasma with 0.5 M ammonium acetate buffer pH 7.4 for 3-days at 37 °C. Hereafter, a liquid-liquid extraction with 1-chlorobutane was performed using paclitaxel as internal standard. Released docetaxel from CriPec® docetaxel nanoparticles was determined in human plasma stabilized with 5 M ammonium acetate, pH 5.0. Hereafter, a liquid-liquid extraction with 1-chlorobutane was performed using docetaxel-d5 in acetonitrile as internal standard. Released docetaxel and its internal standard were eluted. The validated ranges for total docetaxel were 2,000–100,000 ng/mL for the high concentrations and 2–500 ng/mL for the low concentrations and 0.250–100 ng/mL for released docetaxel.In conclusion the newly developed assay met the required standards for validation and was applied successfully to support pharmacokinetic analysis in both serum and tissue in patients treated with Cripec®.