Rapid quantitation of cyclophosphamide metabolites in plasma by liquid chromatography-mass spectrometry.
A method is described for the quantification of two metabolites of cyclophosphamide, specifically 4-hydroxycyclophosphamide (HCy), and carboxyethylphosphoramide mustard (CEPM). Plasma HCy is derivatized to the phenylhydrazone which is quantitated by LC-MS monitoring the chloride adduct of the derivative. The LLOQ based on material applied to the system is approximately 20 fmol. Plasma CEPM concentration is determined using LC-MS with a deuterated internal standard. Both assays have 50-fold dynamic range and require less than 4h to complete. The development of this rapid analytical method makes it feasible to adjust the dose of cyclophosphamide based on the pharmacokinetic disposition of HCy and CEPM in hopes of decreasing nonrelapse mortality in cancer patients.
University of Washington Mass Spectrometry Center, Box 357610, Seattle, 98195, USA.
Thomas F
TF
Kalhorn
William N
WN
Howald
Scott
S
Cole
Brian
B
Phillips
Joanne
J
Wang
John T
JT
Slattery
Jeannine S
JS
McCune
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism; D004355:Drug Stability; D013058:Mass Spectrometry / Q000379:methods*; D010752:Phosphoramide Mustards / Q000097:blood; D015203:Reproducibility of Results
D010752:Phosphoramide Mustards; C445000:carboxyethylphosphoramide mustard; C012358:4-hydroxycyclophosphamide; D003520:Cyclophosphamide