Quantification of cidofovir in human serum by LC-MS/MS for children.
A new method for the quantification of cidofovir (CDV), an acyclic nucleotide analogue of cytosine with antiviral activity against a broad-spectrum of DNA viruses, in human serum, using high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has been developed. A strong anion exchange (SAX) solid-phase extraction procedure was applied for the sample preparation. The tandem mass spectrometer was tuned in the multiple reaction monitoring mode to monitor the m/z 278.1-->234.9 and the m/z 288.1-->133.1 transitions for CDV and the internal standard 9-(2-phosphonylmethoxyethyl)guanine (PMEG), respectively, using negative electrospray ionization. The MS/MS response was linear over the concentration range from 78.125 ng/ml to 10,000 ng/ml, with a lower limit of quantification of 78.125 ng/ml. The intra- and inter-day precisions (relative standard deviation (%)) for CDV were less than 7.8% and the accuracies (% of deviation from nominal level) were within +/-12.1% for quality controls. The novel LC-MS/MS method allowed a specific, sensitive and reliable determination of CDV in human serum and was applied to investigate the yet unknown pharmacokinetic properties of CDV in a paediatric cancer patient.
Breddemann
André
A
Department of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-University of Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
Hsien
Linda
L
Tot
Edith
E
Läer
Stephanie
S
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D063065:Organophosphonates / Q000097:blood* / Q000737:chemistry; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir