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Measurement of total and free docetaxel concentration in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry.
J Pharm Biomed Anal. 2016 Jan 05; 117:140-9.JP

Abstract

Docetaxel is a semi-synthetic taxane with cytotoxic anti-neoplastic activity and, currently used as anticancer agent in several types of cancer. Docetaxel is highly bound to plasma proteins, and this significantly determines its clearance and activity. Therefore, measurement of free docetaxel in plasma is pharmacologically important when pharmacokinetics is investigated. We developed and validated chromatographic methods by ultra-performance liquid chromatography-tandem mass spectrometry to measure total and free docetaxel concentration in human plasma. The final validated methods involved liquid-liquid extraction followed by dryness under nitrogen evaporation. To measure free docetaxel concentration, sample preparation was preceded by ultrafiltration. Chromatographic separation was achieved using an Acquity(®) UPLC(®) BEH™ (2.1×100 mm id, 1.7 μm) reverse-phase C18 column at a flow rate of 0.4 mL/min, using isocratic elution mode containing ammonium acetate/formic acid in water/methanol (30:70 v/v) as mobile phase. Docetaxel and its internal standard (paclitaxel) were detected by electrospray ionization mass spectrometry in positive ion multiple reaction monitoring mode using mass-to-charge (m/z) transitions of 808.3→527.0 (quantifier) and 808.3→509.0 (qualifier); and 854.3→569.0 (quantifier) and 854,3→509,0 (qualifier), respectively. The run time per sample was 3.5 min. The limits of quantification were 1,95 and 0.42 μg/L and linearity was observed between 1.95 and 1000 and 0.42-100 μg/L for total and free docetaxel, respectively. Coefficients of variation and absolute relative biases were less than 13.8% and 10.0%. Recovery values were greater than 79.4%. Evaluation of the matrix effect showed ion suppression and no carry-over was observed. The validated methods could be useful for both therapeutic drug monitoring and pharmacokinetic studies. They could be applied to daily clinical laboratory practice to measure the concentration of total and free docetaxel in plasma.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Rigo-Bonnin R
Laboratori Clínic Department, IDIBELL, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address: raulr@bellvitgehospital.cat.
Cobo-Sacristán S
Pharmacy Department, IDIBELL, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Gonzalo-Diego N
Pharmacy Department, IDIBELL, Catalan Institute of Oncology, Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain.
Colom H
Department of Biopharmaceutics and Pharmacokinetics, School of Pharmacy, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Muñoz-Sánchez C
Pharmacy Department, IDIBELL, Catalan Institute of Oncology, Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain.
Urruticoechea A
Catalan Institute of Oncology, IDIBELL, Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain.
Falo C
Catalan Institute of Oncology, IDIBELL, Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain.
Alía P
Laboratori Clínic Department, IDIBELL, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.

MeSH

Antineoplastic AgentsChromatography, High Pressure LiquidDocetaxelHumansTandem Mass SpectrometryTaxoidsUltrafiltration

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26350560

Citation

Rigo-Bonnin, Raül, et al. "Measurement of Total and Free Docetaxel Concentration in Human Plasma By Ultra-performance Liquid Chromatography-tandem Mass Spectrometry." Journal of Pharmaceutical and Biomedical Analysis, vol. 117, 2016, pp. 140-9.
Rigo-Bonnin R, Cobo-Sacristán S, Gonzalo-Diego N, et al. Measurement of total and free docetaxel concentration in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2016;117:140-9.
Rigo-Bonnin, R., Cobo-Sacristán, S., Gonzalo-Diego, N., Colom, H., Muñoz-Sánchez, C., Urruticoechea, A., Falo, C., & Alía, P. (2016). Measurement of total and free docetaxel concentration in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis, 117, 140-9. https://doi.org/10.1016/j.jpba.2015.08.025
Rigo-Bonnin R, et al. Measurement of Total and Free Docetaxel Concentration in Human Plasma By Ultra-performance Liquid Chromatography-tandem Mass Spectrometry. J Pharm Biomed Anal. 2016 Jan 5;117:140-9. PubMed PMID: 26350560.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Measurement of total and free docetaxel concentration in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry. AU - Rigo-Bonnin,Raül, AU - Cobo-Sacristán,Sara, AU - Gonzalo-Diego,Núria, AU - Colom,Helena, AU - Muñoz-Sánchez,Carmen, AU - Urruticoechea,Ander, AU - Falo,Catalina, AU - Alía,Pedro, Y1 - 2015/08/28/ PY - 2015/04/14/received PY - 2015/08/18/revised PY - 2015/08/19/accepted PY - 2015/9/10/entrez PY - 2015/9/10/pubmed PY - 2016/9/13/medline KW - Free docetaxel KW - Paclitaxel KW - Total docetaxel KW - UPLC–MS/MS KW - Ultrafiltration SP - 140 EP - 9 JF - Journal of pharmaceutical and biomedical analysis JO - J Pharm Biomed Anal VL - 117 N2 - Docetaxel is a semi-synthetic taxane with cytotoxic anti-neoplastic activity and, currently used as anticancer agent in several types of cancer. Docetaxel is highly bound to plasma proteins, and this significantly determines its clearance and activity. Therefore, measurement of free docetaxel in plasma is pharmacologically important when pharmacokinetics is investigated. We developed and validated chromatographic methods by ultra-performance liquid chromatography-tandem mass spectrometry to measure total and free docetaxel concentration in human plasma. The final validated methods involved liquid-liquid extraction followed by dryness under nitrogen evaporation. To measure free docetaxel concentration, sample preparation was preceded by ultrafiltration. Chromatographic separation was achieved using an Acquity(®) UPLC(®) BEH™ (2.1×100 mm id, 1.7 μm) reverse-phase C18 column at a flow rate of 0.4 mL/min, using isocratic elution mode containing ammonium acetate/formic acid in water/methanol (30:70 v/v) as mobile phase. Docetaxel and its internal standard (paclitaxel) were detected by electrospray ionization mass spectrometry in positive ion multiple reaction monitoring mode using mass-to-charge (m/z) transitions of 808.3→527.0 (quantifier) and 808.3→509.0 (qualifier); and 854.3→569.0 (quantifier) and 854,3→509,0 (qualifier), respectively. The run time per sample was 3.5 min. The limits of quantification were 1,95 and 0.42 μg/L and linearity was observed between 1.95 and 1000 and 0.42-100 μg/L for total and free docetaxel, respectively. Coefficients of variation and absolute relative biases were less than 13.8% and 10.0%. Recovery values were greater than 79.4%. Evaluation of the matrix effect showed ion suppression and no carry-over was observed. The validated methods could be useful for both therapeutic drug monitoring and pharmacokinetic studies. They could be applied to daily clinical laboratory practice to measure the concentration of total and free docetaxel in plasma. SN - 1873-264X UR - https://www.unboundmedicine.com/medline/citation/26350560/Measurement_of_total_and_free_docetaxel_concentration_in_human_plasma_by_ultra_performance_liquid_chromatography_tandem_mass_spectrometry_ DB - PRIME DP - Unbound Medicine ER -