On-Line Determination of Cyclophosphamide in Blood Samples Utilizing Microextraction by Packed Sorbent and Liquid Chromatography Tandem Mass Spectrometry (MEPS-LC-MS/MS)

Microextraction by packed sorbent (MEPS) was used to handle whole mice blood samples. MEPS was used as an online rapid sample-preparation method, followed by liquid chromatography with tandem mass spectrometry (LC- MS/MS). Cyclophosphamide in mice blood was used as a model compound. The new method reduced the handling time and the cost and could handle small volumes of whole blood samples (20 μL). The lower limit of quantification (LLOQ) was 0.1μg/mL. The accuracy of the quality-control (QC) samples ranged from 107 to 110 %. The within-day variation was within the range 2.0-7.0% (C.V.%) while the between-day variation was between 4.0 and 6.0% (C.V.%). The calibra- tion curve in whole blood was constructed within the concentration range 0.1-100 μg/mL. The coefficients of determina- tion (R 2 ) were > 0.99 (n = 3). The present method is rapid, reliable and accurate and may be used for therapeutic drug monitoring of cyclophosphamide in whole blood. The method was applied for preclinical study of cyclophosphamide in mice.