TY - JOUR
T1 - The development and clinical validation of a turbulent-flow liquid chromatography-tandem mass spectrometric method for the rapid quantitation of docetaxel in serum
AU - Marzinke, Mark A.
AU - Breaud, Autumn R.
AU - Clarke, William
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/2/8
Y1 - 2013/2/8
N2 - Background: Docetaxel is a second generation taxane utilized as an anti-neoplastic agent in cancer chemotherapies. Traditional treatment regimens have resulted in significant adverse effects, resulting in the shift to more frequent drug administration at lower doses. As a result, it is important to monitor serum docetaxel concentrations to optimize efficacy and minimize adverse effects. Methods: Serum containing docetaxel was combined with acetonitrile containing deuterated internal standard, and following protein precipitation, supernatant was diluted with water for on-line sample extraction. Following turbulent-flow chromatography (TFC), analytic separation was achieved on a Hypersil Gold C-18 (50 × 2.1. mm) column and the eluent analyzed using a TSQ Vantage mass spectrometer with selected reaction monitoring. Matrix effects were characterized in addition to carryover, precision, linearity, recovery and functional sensitivity. Results: The simple and complex precision for the assay at multiple concentrations was ≤ 6.2%. The assay has functional sensitivity of < 3. ng/ml, and is linear from 8.1 to 1978. ng/ml. Method comparison studies with a reference HPLC-MS/MS method show a slope of 0.84 with a Spearman coefficient of 0.99. Conclusions: Based on the validation metrics, we have generated a sensitive and automated TFC-MS/MS method for docetaxel quantitation in serum.
AB - Background: Docetaxel is a second generation taxane utilized as an anti-neoplastic agent in cancer chemotherapies. Traditional treatment regimens have resulted in significant adverse effects, resulting in the shift to more frequent drug administration at lower doses. As a result, it is important to monitor serum docetaxel concentrations to optimize efficacy and minimize adverse effects. Methods: Serum containing docetaxel was combined with acetonitrile containing deuterated internal standard, and following protein precipitation, supernatant was diluted with water for on-line sample extraction. Following turbulent-flow chromatography (TFC), analytic separation was achieved on a Hypersil Gold C-18 (50 × 2.1. mm) column and the eluent analyzed using a TSQ Vantage mass spectrometer with selected reaction monitoring. Matrix effects were characterized in addition to carryover, precision, linearity, recovery and functional sensitivity. Results: The simple and complex precision for the assay at multiple concentrations was ≤ 6.2%. The assay has functional sensitivity of < 3. ng/ml, and is linear from 8.1 to 1978. ng/ml. Method comparison studies with a reference HPLC-MS/MS method show a slope of 0.84 with a Spearman coefficient of 0.99. Conclusions: Based on the validation metrics, we have generated a sensitive and automated TFC-MS/MS method for docetaxel quantitation in serum.
KW - Assay validation
KW - Docetaxel
KW - LC-MS/MS
KW - Turbulent-flow chromatography
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U2 - 10.1016/j.cca.2012.11.021
DO - 10.1016/j.cca.2012.11.021
M3 - Article
C2 - 23200823
AN - SCOPUS:84871870071
SN - 0009-8981
VL - 417
SP - 12
EP - 18
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
ER -