Quantification of CLR1401, a novel alkylphosphocholine anticancer agent, in rat plasma by hydrophilic interaction liquid chromatography-tandem mass spectrometric detection.
A rapid and specific LC-MS/MS based bioanalytical method was developed and validated for the determination of 18-(p-iodophenyl)octadecyl phosphocholine (CLR1401), a novel phosphocholine drug candidate, in rat plasma. The optimal chromatographic behavior of CLR1401 was achieved on a Kromasil silica column (50 mm x 3 mm, 5 microm) under hydrophilic interaction chromatography. The total LC analysis time per injection was 2.8 min with a flow rate of 1.5 mL/min under gradient elution. Liquid-liquid extraction in a 96-well format using ethyl acetate was developed and applied for method validation and sample analysis. The method validation was conducted over the curve range of 2.00-1000 ng/mL using 0.0500 mL of plasma sample. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels showed < or = 5.9% relative standard deviation (RSD) and -10.8 to -1.4% relative error (RE). The method was successfully applied to determine the toxicokinetics of CLR1401 in rats from three dose groups of 0.4, 4.0, and 10.0 mg/kg/day via intravenous administration.
Jiang
Hongliang
H
Department of Bioanalytical Chemistry, Covance Laboratories Inc., 3301 Kinsman Boulevard, Madison, WI 53704, USA. Hongliang.Jiang@Covance.com
Cannon
Michelle J
MJ
Banach
Maria
M
Pinchuk
Anatoly N
AN
Ton
Giangthy N
GN
Scheuerell
Christie
C
Longino
Marc A
MA
Weichert
Jamey P
JP
Tollefson
Richard
R
Clarke
William R
WR
Ji
Qin C
QC
Jiang
Xiangyu
X
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D057927:Hydrophobic and Hydrophilic Interactions; D016018:Least-Squares Analysis; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
C509923:18-(4-iodophenyl)octadecylphosphocholine; D000970:Antineoplastic Agents; D010767:Phosphorylcholine