Drugs modulating the metabotropic glutamate type 2 receptor (mGluR₂) activity may have therapeutic benefits in treating a large spectrum of neuro-psychiatric disorders, from schizophrenia to Parkinson's disease, both as a symptomatic therapy and potential disease-modifying paradigm. LY-487,379 is a highly selective mGluR₂ positive allosteric modulator that is widely used to study mGluR₂ function using experimental animal models. The common marmoset is a small primate that has long been used in neuroscience. However, given its small size and small circulating blood volume, conducting studies to determine the PK profile of LY-487,379 is challenging. We developed and validated a sensitive and selective analytical method that enables quantification of LY-487,379 using a limited volume of plasma (10 μL). The analytical method consists of protein precipitation followed by high-performance liquid chromatography with heat assisted electrospray ionization mass spectrometry (HPLC-HESI-MS/MS). The chromatographic separation was achieved using gradient elution with a mobile phase consisting of acetonitrile and 0.01% formic acid in water on a Thermo Scientific Aquasil C18 analytical column (100 × 2.1 mm I.D., 5 μm) operating at 40 °C and at a flow rate of 300 μL/min. The method displays a linear relationship ranging from 0.2 to 100 ng/mL. Intra- and inter-day relative standard deviations are <1.4% and 7.9%, respectively and the relative error ranged from −6.9 to 9.7%. The method was used to quantify LY-487,379 in both rat and marmoset plasma, and PK parameters were determined after a single subcutaneous dose of 1.0 mg kg⁻¹ in both species and significant differences in C_max, AUC and T_1/2 were observed.

调节代谢型谷氨酸2型受体（mGluR ₂）活性的药物，作为对症治疗和潜在的疾病改良范例，可以治疗从精神分裂症到帕金森氏症的各种神经精神疾病。LY-487,379是一种高度选择性的mGluR ₂阳性变构调节剂，被广泛用于研究mGluR ₂使用实验动物模型的功能。普通mar猴是一种小型灵长类动物，长期以来一直用于神经科学。然而，鉴于其体积小和循环血量少，进行研究以确定LY-487,379的PK曲线具有挑战性。我们开发并验证了一种灵敏且选择性的分析方法，该方法可使用有限体积的血浆（10μL）对LY-487,379进行定量。分析方法包括蛋白质沉淀，高效液相色谱和热辅助电喷雾电离质谱（HPLC-HESI-MS / MS）。色谱分离是通过在Thermo Scientific上使用由乙腈和0.01％甲酸水溶液组成的流动相进行梯度洗脱实现的Aquasil C18分析柱（100×2.1 mm内径，5μm）在40°C和300μL/ min的流速下运行。该方法显示的线性关系为0.2到100 ng / mL。日内和日间相对标准偏差分别＜1.4％和7.9％，相对误差范围为-6.9至9.7％。该方法用于定量大鼠和mar猴血浆中的LY-487,379，并且在两种物种的单次皮下剂量1.0 mg kg ^-1后测定PK参数，并观察到C _max，AUC和T _1/2的显着差异。