Quantification of cidofovir in human serum by LC–MS/MS for children

Primary HHV 6 infection after liver transplantation with acute graft rejection and multi‐organ failure: Successful treatment with a 2.5‐fold dose of cidofovir and reduction of immunosuppression

“…We had chosen cidofovir because of a report of treatment failure of ganciclovir and foscarnet but successful treatment with cidofovir in a patient with pediatric cancer (12). Additionally, we had the opportunity of measuring a plasma concentration profile of cidofovir with a recently established high‐performance liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS) (13). This was important because sufficient pharmacokinetic data of cidofovir in children were not available at that time but it could be assumed that maturation and growth affect the pharmacokinetics of cidofovir (14, 15).…”

Determination of cidofovir in human plasma after low dose drug administration using high-performance liquid chromatography–tandem mass spectrometry

“…Low doses of CDV (representing 5-10% of the FDA approved dose for CMV retinitis) are typically used in this population due to the drug’s nephrotoxicity. Although an LC-MS/MS assay has been published previously, its suitability for clinical pharmacokinetic studies of low dose CDV is decreased by the lack of a commercially available internal standard and insufficient sensitivity [15]. The method described in the current manuscript is adequately sensitive to characterize systemic drug exposure following low dose CDV administration and capable of being implemented in laboratories with standard LC-MS instrumentation.…”

“…In order to elucidate the pharmacokinetics and pharmacodynamics of CDV used for the treatment of BKVN in kidney transplant recipients, it was necessary to develop a sensitive and specific assay method for the determination of CDV in human plasma. To date, four HPLC methods and one LC-MS/MS method have been described in the literature [11-15]. The HPLC methods require a large blood volume making intensive sampling difficult, or involve a laborious pre-column fluorescence derivatization process.…”

“…Further, due to the low dose of CDV used in the renal transplant population, the published LC-MS/MS method, with a selective detection in the range of 78.125-10,000 ng/ml requiring 300 μl serum, cannot be used. [15]. This method is also difficult to reproduce as it employs an internal standard that is not commercially available.…”

Therapeutic drug monitoring by LC–MS–MS with special focus on anti-infective drugs

“…For quantitative determination of cidofovir, a nucleotide analogue which is approved for the therapy of CMV retinitis in AIDS patients, Breddemann et al [70] developed a method which was used for a pharmacokinetic study in paediatric cancer patients. With solid-phase extraction of 0.3 mL serum, an analytical range from 0.0078-10 mgL −1 could be achieved.…”