盐酸美法仑光降解杂质的鉴定与含量测定

陈雪琴; 高芳; 廖明毅; 李瑞; 李薇; 丁黎

doi:10.11665/j.issn.1000-5048.20170514

盐酸美法仑光降解杂质的鉴定与含量测定

Identification and determination of the photodegradation impurities in melphalan hydrochloride

摘要

摘要: 对盐酸美法仑的光降解杂质PD1和PD2进行结构鉴定，并对PD1和PD2建立含量测定方法。通过LC-MS/MS法推测光降解杂质的结构，合成相应杂质，通过杂质比对确认光降解杂质。建立亲水作用色谱法对PD1和PD2进行含量测定，色谱柱为Atlantis HILIC柱(4.6 mm×150 mm，3 μm)，流动相为0.1 mol/L甲酸铵溶液(甲酸调pH为3.0)-乙腈(13∶87)，流速为1.0 mL/min，柱温为35 ℃，检测波长为260 nm。结果显示:光降解杂质PD1为4-氨基-L-苯丙氨酸盐酸盐，PD2为4-(2-氯乙基氨基)-L-苯丙氨酸盐酸盐；在建立的亲水作用色谱法中，盐酸美法仑与PD1、PD2可完全分离，建立的方法可用于光降解杂质的含量测定。

Abstract: This study was aimed to identify the photodegradation impurities(PD1 and PD2)in melphalan hydrochloride and establish a method for determining PD1 and PD2. The structures of the photodegradation impurities were inferred by LC-MS/MS. The impurities were confirmed by comparing with synthesized impurities. An HILIC method was established to determine PD1 and PD2. The method was carried out on an Atlantis HILIC column(4. 6 mm×150 mm, 3 μm)with the mobile phase consisting of 0. 1 mol/L ammonium formate(adjusted to pH 3. 0 with formic acid)and acetonitrile(13∶87)at the flow rate of 1. 0 mL/min. The column temperature was 35 °C. The detection wavelength was 260 nm. PD1 and PD2 were characterized as 4-amino-L-phenylalanine hydrochloride and 4-(2-chloroethyl)amino-L-phenylalanine hydrochloride, respectively. Melphalan hydrochloride, PD1 and PD2 were separated completely under the HILIC condition. The established HILIC method can be used to determine the photodegradation impurities.

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