Development and validation of LC-MS/MS method for quantitative determination of (-)-securinine in mouse plasma.
(-)-Securinine (SE) is a major alkaloid found in plant Securinega suffruticosa, which has a wide range of pharmacological activities including anticancer, anti-parasitic and central nervous system stimulating effects, etc. To aid the pharmacological study of SE, we developed an LC-MS/MS method for quantitative determination of SE in mouse plasma. In this method, plasma samples were first prepared with salting-out assisted liquid-liquid extraction using cold acetonitrile (-20°C) and 2.00 M ammonium acetate. Separation of SE and the internal standard (IS) from sample matrix was achieved on a Gemini Nx C18 column using 40% acetonitrile and 60% 10.0mM ammonium acetate at a flow rate of 0.200 mL min(-1). Quantification of SE was accomplished with positive electrospray ionization tandem mass spectrometry using mass transitions m/z 218.1→84.1 for SE, and m/z 204.1→70.2 for the IS. This method has a lower limit of quantitation (LLOQ) of 0.600 ng mL(-1) and a linear calibration range up to 600 ng mL(-1) in mouse plasma. The intra- and inter-run accuracy (%RE) and precision (%CV) were ≤ ± 6% and 6%, respectively. The IS normalized matrix factors from six lots of plasma matrices ranged 0.92-1.07, and the recoveries of plasma SE were 99-109%. The validated method has been applied to the measurement of SE in plasma samples of a mouse study.
Department of Chemistry, Cleveland State University, Cleveland, OH 44115, United States.
Simuli L
SL
Wabuyele
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, United States.
David
D
Wald
Department of Chemistry, Cleveland State University, Cleveland, OH 44115, United States; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, United States. Electronic address: y.xu@csuohio.edu.
Yan
Y
Xu
D000818:Animals; D001381:Azepines / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D006572:Heterocyclic Compounds, Bridged-Ring / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D007783:Lactones / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D016014:Linear Models; D059625:Liquid-Liquid Extraction; D051379:Mice; D008807:Mice, Inbred BALB C; D010880:Piperidines / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012995:Solubility; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
D001381:Azepines; D006572:Heterocyclic Compounds, Bridged-Ring; D007783:Lactones; D010880:Piperidines; C000785:securinine
LC–MS/MS; Method validation; Myeloid differentiation inducing agent; Norsecurinine; Salting-out assisted liquid–liquid extraction; Securinine