首页> 外文期刊>Chromatographia >LC-MS-MS determination of cyclo{(2S)-2-amino-8-[(aminocarbonyl) hydrazono]decanoyl-1-L-tryptophyl-L-isoleucyl-(2R)-2-piperidinecarbonyl} a novel histone deacetylase inhibitor in rat serum
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LC-MS-MS determination of cyclo{(2S)-2-amino-8-[(aminocarbonyl) hydrazono]decanoyl-1-L-tryptophyl-L-isoleucyl-(2R)-2-piperidinecarbonyl} a novel histone deacetylase inhibitor in rat serum

机译:LC-MS-MS测定新型组蛋白脱乙酰基酶抑制剂环{(2S)-2-氨基-8-[(氨基羰基)肼基]癸酰-1-L-色氨酸-L-异亮氨酰-(2R)-2-哌啶基羰基}在大鼠血清中

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摘要

A rapid and sensitive liquid chromatography-tandem mass spectrometry assay was developed for the determination of a novel histone deacetylase inhibitor, cyclo{(2S)-2-amino-8[(aminocarbonyl)hydrazono]decanoyl-1-L-tryptophyl-L-isoleucyl-(2R)-2-piperidinecarbonyl} (SD-2007), in rat serum. The mobile phase consisted of acetonitrile and ammonium formate (10 mM) (85: 15 v/v), and the flow rate was 0.25 mL min(-1). Chromatographic separations were achieved by isocratic elution on a C-18 column. Multiple reaction monitoring was based on the transition of m/z = 681.8 -> 83.6 for SD-2007 and 372.1 -> 176.1 for trazodone (internal standard). A linearity was observed over a concentration range from 2 to 1,000 ng mL(-1) (r(2) > 0.999), with the lower limit of quantification at 2 ng mL(-1) with 100 mu L of rat serum. The mean intra- and inter-day assay accuracy ranged from 98.5-109.7% to 95.2-102.7%, respectively, and the mean intra- and inter-day precision was between 4.3-11.3% and 2.9-13.3%. The developed assay was applied to a pharmacokinetic study of SD-2007 in rats after intravenous injection (dose 4 mg kg(-1)).
机译:建立了一种快速灵敏的液相色谱-串联质谱分析法,用于测定新型组蛋白脱乙酰基酶抑制剂,环{(2S)-2-氨基-8 [(氨基羰基)肼基]癸酰-1-L-色氨酸-L-大鼠血清中的异亮氨酰-(2R)-2-哌啶羰基}(SD-2007)。流动相由乙腈和甲酸铵(10 mM)(85:15 v / v)组成,流速为0.25 mL min(-1)。色谱分离是通过在C-18柱上进行等度洗脱实现的。多重反应监测基于SD-2007的m / z = 681.8-> 83.6的转变和曲唑酮(内标)的372.1-> 176.1的转变。在2至1,000 ng mL(-1)的浓度范围内观察到线性度(r(2)> 0.999),对100μL大鼠血清的定量下限为2 ng mL(-1)。日内和日间分析的平均准确度分别为98.5-109.7%至95.2-102.7%,日间和日间平均准确度在4.3-11.3%和2.9-13.3%之间。这项开发的测定方法用于大鼠静脉注射(剂量4 mg kg(-1))后SD-2007的药代动力学研究。

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