Development of a liquid chromatography/tandem mass spectrometry assay for the quantification of Aplidin, a novel marine-derived antineoplastic agent, in human plasma.
A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay was developed and validated to quantify a novel marine-derived depsipeptide, Aplidin, in human plasma. The method was validated to demonstrate the specificity, recovery, limit of quantitation (LOQ), accuracy, and precision of measurements. The calibration range for Aplidin was established using Aplidin standards from 0.05-50 ng/mL in blank human plasma. The multiple reaction monitoring, based on the transition m/z 1110.7 --> 295.3, was specific for Aplidin, and that based on the transition m/z 1112.6 --> 297.3 was specific for didemnin B (the internal standard); no endogenous materials interfered with the analysis of Aplidin and didemnin B from blank human plasma. The assay was linear over the concentration range 0.05-50.0 ng/mL. The correlation coefficients for the calibration curves ranged from 0.9979 to 0.9999. The mean intra- and interday accuracies for all calibration standards (n = 12) ranged from 97 to 106% (</=6% bias), and the mean interday precision for all calibration standards was less than 8.3%. The mean intra- and interday assay accuracy for all quality control replicates (n = 12), determined at each QC level throughout the validated runs, remained below 12 and 7%, respectively. The mean intra- and interday assay precision was less than 13.1 and 10.7% for all QC levels, respectively. The assay is currently used to measure Aplidin plasma concentrations to support clinical trials.
Yin
Jianming
J
PharmaMar USA, Inc., 320 Putnam Avenue, Cambridge, MA 02139-4616, USA. jyin@pharmamarusa.com
Aviles
Pablo
P
Lee
William
W
Ly
Carl
C
Floriano
Pablo
P
Ignacio
Manzanares
M
Faircloth
Glynn
G
D000970:Antineoplastic Agents / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D047630:Depsipeptides; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D010456:Peptides, Cyclic / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C098980:plitidepsin