Kinetics of Phosphoramide Mustard Hydrolysis in Aqueous Solution

Development and validation of LC–MS/MS assays for the quantification of bendamustine and its metabolites in human plasma and urine

“…Literature on the stability of nitrogen mustard-containing compounds like melphalan and chlorambucil describes that these compounds are more stable at a pH <3 [4], when treated on ice-water instead of at room temperature [7,8] and in the presence of 5% human serum albumin or human plasma as compared to aqueous buffers [9]. This led to the idea to stabilize bendamustine by a 100-fold dilution with human plasma.…”

Novel Melphalan and Chlorambucil Derivatives of 2,2,6,6-Tetramethyl-1-piperidinyloxy Radicals: Synthesis, Characterization, and Biological Evaluation <i>in Vitro</i>

“…21) The major hydrolytic pathway of the alkylating agents was the formation of the aziridinium ion, followed by a rapid hydrolysis to yield the monohydroxy, and subsequently the dihydroxy products. All hydrolysis profiles were found to exhibit linear relationships (RϾ0.96) in our assays.…”

Gas chromatography–electron ionization mass spectrometry and liquid chromatography–electrospray tandem mass spectrometry for determination of impurities in the anti-cancer drug isophosphoramide mustard

“…and the packing particle size was 10 m. The HPLC system was operated isocratically at a flow rate of 3.0 ml/min. The mobile phase was prepared as 0.005 M perchloric acid (Aldrich, Milwaukee, WI) in HPLC-grade water to give pH 2.1 [6]. The detector was set at 206 nm for the detection of intact IPM and possible impurities.…”

“…While the pharmacokinetics of CPA and PM have been well investigated, few reports on the pharmacokinetics of IPM have appeared in the literature [6][7][8]. Similar to PM, IPM has hydrolytic pathways that apparently follow first-order kinetics; at 38 • C the half-life of IPM was 45 min in aqueous phosphate buffer of pH 7.4, while at pH 1.7 the half-life increased to 128 min [9].…”

“…Isophosphoramide mustard (IPM), a metabolite of ifosfamide, is being readied for clinical trials [1][2][3][4][5][6][7][8][9][10][11][12]. Studies with IPM suggest that the agent has improved anticancer activities in standard animal models, when compared to phosphoramide mustard (PM) and other mustards, ifosfamide and cyclophosphamide (CPA) [9,12].…”