High-performance liquid chromatographic assay for mitoxantrone in plasma using electrochemical detection.
A sensitive and specific high-performance liquid chromatographic (HPLC) assay was developed for the quantitation of mitoxantrone in plasma using electrochemical detection. Bisantrene was chosen as the internal standard. A reversed-phase, 10-microns muBondapak C18 analytical column (30 cm X 3.9 mm) with an isocratic mobile phase of 28% acetonitrile in 80 mM sodium formate buffer (pH 3.0) was used. The eluent was monitored by both electrochemical detection at an applied potential of +0.75 V vs. Ag/AgCl and visible absorbance at 660 nm. Only electrochemical detection was able to quantitate the internal standard and provided ten times higher sensitivity than visible absorbance for mitoxantrone with a detection limit as low as 0.1 ng/ml. Calibration curves in the range 0.1-1000 ng/ml showed good linearity (r = 0.998) and precision (coefficient of variation less than 10%). This HPLC method utilized a reproducible and inexpensive liquid-liquid extraction procedure. Using methylene chloride, the extraction efficacy of mitoxantrone from plasma was 85.3% with a coefficient of variation less than 2.1%. This new assay was then applied to measure mitoxantrone concentrations in plasma obtained from two leukemic patients receiving 12 mg/m2 mitoxantrone as a 1-h infusion.
Choi
K E
KE
Lynn Sage Clinical Pharmacology Laboratory, University of Chicago, IL.
Sinkule
J A
JA
Han
D S
DS
McGrath
S C
SC
Daly
K M
KM
Larson
R A
RA
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004563:Electrochemistry; D006801:Humans; D007938:Leukemia / Q000097:blood; D008942:Mitoxantrone / Q000097:blood* / Q000493:pharmacokinetics; D013696:Temperature
D008942:Mitoxantrone