TY - JOUR
T1 - High-throughput plasma docetaxel quantification by liquid chromatography-tandem mass spectrometry
AU - Corona, Giuseppe
AU - Elia, Caterina
AU - Casetta, Bruno
AU - Frustaci, Sergio
AU - Toffoli, Giuseppe
PY - 2011/1/30
Y1 - 2011/1/30
N2 - Background: The most valuable treatment option for breast, prostate and lung carcinomas is at present represented by a low dose of docetaxel, administered on a weekly basis. A better understanding of docetaxel pharmacokinetic and pharmacodynamic profiles could lead to an improvement in this dose regimen efficacy. Methods: In this study a high-throughput method is described for the rapid quantification of docetaxel for large clinical pharmacology investigations. This analytical approach is based on an automatic on-line purification and enrichment technique followed by a measurement in tandem mass spectrometry through Multiple Reaction Monitoring. Results: The assay was validated over a 0.15-1500ng/mL range. Intra-day precision ranged from 1.9% to 6.4%, while the inter-day was between 7.6% and 11.2%. The mean deviation from the nominal value ranged from -0.5% to 5.6% for the intra-day, and from -0.4% to 3.1% for the inter-day assay. Clinical applicability was demonstrated by measuring plasma pharmacokinetics in patients receiving weekly 25-35mg/m2 of docetaxel. Conclusion: The proposed LC-MS/MS assay was found to have a better performance than previously reported methods in terms of sensitivity and sample preparation. It does not require any laborious pre-analytical manipulation and can be easily employed in large clinical pharmacology studies.
AB - Background: The most valuable treatment option for breast, prostate and lung carcinomas is at present represented by a low dose of docetaxel, administered on a weekly basis. A better understanding of docetaxel pharmacokinetic and pharmacodynamic profiles could lead to an improvement in this dose regimen efficacy. Methods: In this study a high-throughput method is described for the rapid quantification of docetaxel for large clinical pharmacology investigations. This analytical approach is based on an automatic on-line purification and enrichment technique followed by a measurement in tandem mass spectrometry through Multiple Reaction Monitoring. Results: The assay was validated over a 0.15-1500ng/mL range. Intra-day precision ranged from 1.9% to 6.4%, while the inter-day was between 7.6% and 11.2%. The mean deviation from the nominal value ranged from -0.5% to 5.6% for the intra-day, and from -0.4% to 3.1% for the inter-day assay. Clinical applicability was demonstrated by measuring plasma pharmacokinetics in patients receiving weekly 25-35mg/m2 of docetaxel. Conclusion: The proposed LC-MS/MS assay was found to have a better performance than previously reported methods in terms of sensitivity and sample preparation. It does not require any laborious pre-analytical manipulation and can be easily employed in large clinical pharmacology studies.
KW - Docetaxel
KW - LC-MS/MS
KW - On-line extraction
KW - Therapeutic drug monitoring
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U2 - 10.1016/j.cca.2010.11.010
DO - 10.1016/j.cca.2010.11.010
M3 - Article
C2 - 21078312
AN - SCOPUS:78650231840
VL - 412
SP - 358
EP - 364
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
SN - 0009-8981
IS - 3-4
ER -