Simultaneous determination of decitabine and vorinostat (Suberoylanalide hydroxamic acid, SAHA) by liquid chromatography tandem mass spectrometry for clinical studies

Development and validation of a liquid chromatography–tandem mass spectrometry method for quantification of decitabine in rat plasma

“…Decitabine was reported to be easily ionized in the positive ionization mode [6,10,11]. In the present study, decitabine formed predominantly adduct ion [M+Na] + at m/z 251.1 in Q1 fullscan mass spectra in positive ESI interface, while the protonated molecule ion [M+H] + at m/z 229.0 was less than 5% relative abundance of [M+Na] + .…”

“…A bioassay based on L1210 cell killers [7] and a high performance liquid chromatography-ultraviolet (HPLC-UV) method [8,9] have been developed to determine decitabine in human plasma, however, these methods suffered from low sensitivity and poor specificity. Patel et al and Cashen et al [10,11] developed sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods to determine decitabine in human plasma. They used an expensive inhibitor of cytidine deaminase, tetrahydrouridine (THU), to stabilize decitabine in plasma.…”

Decitabine triphosphate levels in peripheral blood mononuclear cells from patients receiving prolonged low-dose decitabine administration: a pilot study

“…A lack of formation, therefore, seems unlikely. More likely, aza-dU and its nucleotides rapidly degrade to other metabolites, such as those proposed by Patel et al [38].…”

“…All samples were immediately placed on ice. A 10 mg/ml tetrahydrouridine solution was added (Wnal concentration of 100 g/ml) to the samples collected after the Wrst cycle to prevent plasma ex vivo deamination of aza-dC [3,38].…”

“…Quantitative determination of aza-dC and its metabolites is, however, analytically challenging because of their instability and low concentrations [25,26,38,40]. As a result, data on the intracellular concentrations of aza-dCTP are extremely sparse [9].…”