Pimavanserin is a new drug approved by the FDA for Parkinson's disease psychosis and other neurological disorders such as Alzheimer's disease. In this study, we developed a UPLC-MS/MS method to quantify pimavanserin disposition in the brain and its pharmacokinetics in mice. Vilazodone was used as the internal standard. Pimavanserin and IS were extracted by liquid-liquid extraction using tert-butyl methyl ether and separated using an Acquity UPLC BEH™ C18 column. The mobile phase consisted of solvent A (0.1% formic acid in acetonitrile) and B (0.1% formic acid in 20 mM ammonium acetate buffer) (A: B, 70:30 v/v) at a flow rate of 0.25 ml/min. The multiple reaction monitoring transitions were performed at m/z 428.23 → 98.15 for pimavanserin and m/z 441.70 > 155.03 for the IS. The developed method was found to be sensitive, fast, and reproducible. The linearity of the method was ˃0.99 over the range of 0.1-300 ng/mL in plasma and 0.25-300 ng/g in the brain homogenate. Precision and accuracy were within the acceptance range. The method was applied to pharmacokinetics and brain uptake studies, which showed that pimavanserin penetrates the blood-brain barrier and reaches a Cmax of 21.9 ± 6.66 ng/g in 2.0 h. We also found that pimavanserin brain to plasma ratio (Kbrain/plasma) is 0.16 ± 0.05 and it is rapidly eliminated.

中文翻译：

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一种快速，简单且高度灵敏的UPLC-MS / MS方法，用于定量测定血浆和组织中的匹马万色林：在小鼠的药代动力学和脑摄取研究中的应用。

Pimavanserin是经FDA批准用于帕金森氏病精神病和其他神经系统疾病（例如阿尔茨海默氏病）的新药。在这项研究中，我们开发了一种UPLC-MS / MS方法来定量确定匹马沙林在大脑中的分布及其在小鼠中的药代动力学。使用维拉唑酮作为内标。通过使用叔丁基甲基醚进行液-液萃取来提取Pimavanserin和IS，并使用Acquity UPLC BEH™C18色谱柱进行分离。流动相由溶剂A（乙腈中的0.1％甲酸）和溶剂B（在20 mM醋酸铵缓冲液中的0.1％甲酸）（A：B，70：30 v / v）组成，流速为0.25 ml / min 。对于匹马沙色林，在m / z 428.23→98.15处进行了多个反应监测转换，对于IS而言，m / z 441.70> 155.03。发现开发的方法灵敏，快速，和可复制的。该方法的线性在血浆中0.1-300 ng / mL和大脑匀浆中0.25-300 ng / g的范围内为˃0.99。精度和准确性均在可接受范围内。该方法用于药代动力学和脑吸收研究，结果表明匹马西林穿透血脑屏障并在2.0小时内达到21.9±6.66 ng / g的Cmax。我们还发现，匹马沙林脑与血浆的比率（Kbrain /血浆）为0.16±0.05，并且可以迅速消除。在2.0小时内达到66 ng / g。我们还发现，匹马沙林脑与血浆的比率（Kbrain /血浆）为0.16±0.05，并且可以迅速消除。在2.0小时内达到66 ng / g。我们还发现，匹马沙林脑与血浆的比率（Kbrain /血浆）为0.16±0.05，并且可以迅速消除。