Comparison of fast liquid chromatography/tandem mass spectrometric methods for simultaneous determination of cladribine and clofarabine in mouse plasma

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 44; no. 2; pp. 492 - 497
• Main Authors: Hsieh, Yunsheng, Duncan, Christine J.G., Lee, Suining, Liu, Ming
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 28-06-2007
• Subjects: Adenine Nucleotides - blood; Animals; Antifungal Agents - blood; Arabinonucleosides - blood; Atmospheric pressure chemical ionization; Chromatography, High Pressure Liquid; Cladribine; Cladribine - blood; Clofarabine; Immunosuppressive Agents - blood; Indicators and Reagents; Ketoconazole - blood; Mass Spectrometry; Mice; Photoionization; Reference Standards; Reproducibility of Results; Ultra performance liquid chromatography; Ultra performance liquid chromatography; Atmospheric pressure chemical ionization; Clofarabine; Photoionization; Cladribine
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2007.02.007

Several fast high performance liquid chromatography/atmospheric pressure ionization/tandem mass spectrometric (HPLC-API/MS/MS) methods were evaluated for the simultaneous determination of cladribine and clofarabine in mouse plasma samples. The chemical separation for analytes under reversed-phase conditions were achieved by using either ultra-performance liquid chromatography (UPLC) or micro-column HPLC coupled to either a quadrupole linear ion trap mass spectrometer (QTrap MS) or a triple quadrupole mass spectrometer. Atmospheric pressure chemical ionization (APCI) or atmospheric pressure photoionization (APPI) interfaces in the positive mode were employed prior to mass spectrometric detection. The effects of various dopant solvents on the APPI sensitivities of analytes and the internal standard were investigated. The matrix ionization suppression potential for the test compounds in plasma samples on fast HPLC-MS/MS methods was examined by a post-column infusion technique. In this work, these proposed approaches were successfully employed to determine the concentrations of cladribine and clofarabine in mouse plasma in the low ng/ml region. The mouse plasma levels of all analytes obtained by these fast HPLC-MS/MS methods were compared and found to be well correlated in terms of analytical accuracy.