The novel sensitive and high throughput determination of cefepime in mouse plasma by SCX-LC/MS/MS method following off-line microElution 96-well solid-phase extraction to support systemic antibiotic programs.
A sensitive and high throughput off-line microElution 96-well solid-phase extraction (SPE) followed by strong cation exchange (SCX) liquid chromatography with tandem mass spectrometry (LC/MS/MS) quantification for determination of cefepime has been developed and validated in mouse plasma. Using the chemical analog, ceftazidime as an internal standard (IS), the linear range of the method for the determination of cefepime in mouse plasma was 4-2048 ng/mL with the lower limit of quantitation level (LLOQ) of 4 ng/mL. The inter- and intra-assay precision and accuracy of the method were below 9.05% and ranged from 95.6 to 113%, respectively, determined by quality control (QC) samples at five concentration levels including LLOQ. After microElution SPE, 71.1% of cefepime was recovered. The application of the validated assay for the determination of cefepime in mouse pharmacokinetics (PK) samples after intravenous (IV) and subcutaneous (SC) doses was demonstrated.
Bu
Wei
W
Anacor Pharmaceuticals, 1020 East Meadow Circle, Palo Alto, CA 94303, USA. wbu@anacor.com
Sexton
Holly
H
Fan
Xiaoqing
X
Torres
Patricia
P
Houston
Paul
P
Heyman
Irwin
I
Liu
Liang
L
D000818:Animals; D000077723:Cefepime; D002511:Cephalosporins / Q000097:blood* / Q000493:pharmacokinetics; D002850:Chromatography, Gel / Q000379:methods*; D005260:Female; D016014:Linear Models; D051379:Mice; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
D002511:Cephalosporins; D000077723:Cefepime