HPLC法测定1,2-环己烷二甲醇中非对映异构体的含量

Content Determination of Diastereoisomer of 1,2-cyclohexanedimethanol by HPLC

目的：建立测定盐酸鲁拉西酮合成中的关键起始原料即1，2-环己烷二甲醇中杂质非对映异构体含量的方法。方法：采用高效液相色谱法。色谱柱为Agilent Rx C8，流动相为0．01mol／L甲酸铵缓冲溶液（pH3．0）-甲醇（70：30），流速为1．0ml／min，检测器为示差折光检测器，检测器温度为35℃，柱温为35℃，以外标法测定。结果：1，2-环己烷二甲醇与其非对映异构体之间分离度大于2．0；二者检测质量浓度线性范围分别为0．01-10．0mg／ml、10．0-200．0gg／ml（r均为0．9999）；非对映异构体平均回收率为99．29％（RSD=0．66％，n=3），检测限为10ng。结论：建立的方法准确、快速，可用于控制终产品盐酸鲁拉西酮中的光学异构体杂质含量。

OBJECTIVE： To establish the method for the content determination of diastereoisomer of 1,2-cyclohexanedimethanol which is the key starting material to synthesis lurasidone hydrochloride by HPLC. METHODS： HPLC method was adopted. The determination was performed on Agilent Rx C8 column with mobile phase consisted of 0.01 mol/L ammonium formate buffer solution （pH 3.0）-methanol （70：30） at the flow rate of 1.0 ml/min. Differential refractive index detector was adopted with the temperature of 35 ℃ .The column temperature was set at 35℃, and external method was used. RESULTS： The resolution of cyclohexanedimethanol and diastereoisomer was greater than 2.0. The linear range of them were 0.01-10.0 mg/ml and 10.0-200.0 pg/ml （r= 0.999 9） ; average recovery of diastereoisomer was greater than 99.29% （RSD=0.66%, n=3）, and the detection limit was 10 ng. CONCLUSIONS： The method is proved to be simple, rapid and suitable for the content control of diastereoisomer in lurasidone hydrochloride.