血清素轉運體 SPECT 造影劑 I-123-ADAM 前驅物 Sn-ADAM 之 HPLC 純度分析方法開發與確效   全文下載

Development and Validation of an HPLC Method for Determination of Purity of Sn-ADAM, a Novel Precursor of Serotonin Transporter SPECT Imaging Agent I-123-ADAM

Sn-ADAM是血清素轉運體（SERTs）單光子放射電腦斷層掃瞄（SPECT）造影劑I-123-ADAM之前驅物與自由態螯合基。本研究利用逆相高效液相層析儀（RP-HPLC），發展Sn-ADAM純度分析方法與分析確效試驗。其最佳層析條件，包括使用Chromolith Performance RP-18e管柱（Merck）、甲醇－乙?－醋酸胺（pH 7.0, 10 mM; 58.8 : 39.2 : 2, v/v/v）移動相與220 nm偵測波長。在線性範圍內（9.9 - 317.8 ppm）之相關係數(r)為0.99997。分析確效試驗之結果，包括專一性、線性範圍、精密度、準確度、LOD/LOQ 、穩定性、耐變性與適用性，均顯示本方法適合作為藥品生產品質控制之分析方法。此外，本研究也利用LC/ESI/MS/MS技術，探討Sn-ADAM與I-127-ADAM之最佳前驅離子－－子離子轉移離子對，並提出Sn-ADAM 、I-127-ADAM與I-123-ADAM之碎片離子結構鑑定與可能之碎裂路徑推測。"

A reversed-phase high performance liquid chromatography (RP-HPLC) method for the purity assay of Sn-ADAM (2-((2-((Dimethylamino)methyl)phenyl)thio)-5-(tri-n-butyltin)-phenylamine) was developed and validated. Sn-ADAM is a precursor and free ligand of I-123-ADAM (I-123-2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine) that is a SPECT imaging agent for serotonin transporters (SERTs). The chromatographic separation for Sn-ADAM was achieved on a RP-18 column with an eluent consisting of methanol-acetonitrile-ammonium acetate (pH 7.0, 10 mM; 58.8 : 39.2 : 2, v/v/v). The absorbance at 220 nm against the concentration of Sn-ADAM was linear over the range of 9.9-317.8 ppm, with a correlation coefficient (r) of 0.99997. Method validation parameters, including specificity, linearity, precision, accuracy, LOD/LOQ, stability, robustness and suitability were evaluated, indicating the potential of this method in pharmaceutical quality control. Moreover, present results of precursor to product ion transitions of Sn-ADAM and I-127-ADAM by LC/ESI/MS/MS provided evidence for identification of fragmentation ions and proposition of the pathways of Sn-ADAM, I-127-ADAM and I-123-ADAM.