文献类型：期刊文献

中文题名：酮苯丙氨酸钙原料药有关物质的鉴定与含量测定

英文题名：Identification and Quantitative Analysis of Related Substances in α-Ketophenylalanine Calcium

作者：潘晨[1];付迪[1];张兆利[2];杨帅兵[2];徐志珍[1];张文清[1];夏玮[1]

机构：[1]华东理工大学上海市功能性材料化学重点实验室,上海200237;[2]上海景峰制药股份有限公司,上海201908

年份：2015

卷号：34

期号：4

起止页码：414

中文期刊名：分析测试学报

外文期刊名：Journal of Instrumental Analysis

收录：CSTPCD;;北大核心:【北大核心2014】；CSCD:【CSCD2015_2016】；

基金：上海市宝山区科学技术委员会产学研合作项目(bkw2013137)

语种：中文

中文关键词：酮苯丙氨酸钙;有关物质;高效液相色谱-四极杆飞行时间质谱;反相高效液相色谱法

外文关键词：α-ketophenylalanine calcium（KTP）; related substances; high performance liquid chromatography / quadrupole time-of-flight mass spectrometry; reversed-phase high performance liquid chromatography

摘要：采用高效液相色谱-四极杆飞行时间质谱（HPLC/QTOF-MS）对酮苯丙氨酸钙原料药中的有关物质进行鉴定,并采用反相高效液相色谱法（RP/HPLC）测定有关物质的含量。有关物质含量测定采用C18色谱柱（4.6 mm×150 mm,5μm）,20 mmol·L-1磷酸二氢钾（磷酸调至p H 3.3）-乙腈（85∶15）为流动相等度洗脱,流速1 m L·min^-1,检测波长205 nm,柱温30℃,进样量10μL。结果确证了2个有关物质分别为苯甲酸和苯乙酸。在优化的色谱条件下,苯甲酸和苯乙酸分别在0.64-5.76μg·m L^-1（r=0.999 6）和0.65-5.82μg·m L^-1（r=0.999 5）范围内线性关系良好,检出限分别为1.3 ng和1.6 ng,平均回收率（n=9）分别为99.6%和99.0%,相对标准偏差分别为1.6%和1.5%。结果表明,HPLC/QTOF-MS可以快速鉴定酮苯丙氨酸钙中的有关物质。本方法灵敏度高、重现性好、准确可靠,可用于酮苯丙氨酸钙原料药有关物质的检测分析及质量控制。
A high performance liquid chromatography / quadrupole time-of-flight mass spectrometric（HPLC /QTOF- MS） method was adopted to identify the related substances in α-ketophenylalanine calcium（ KTP） and a reversed-phase high performance liquid chromatographic（ RP / HPLC） method was established for the quantitative determination of its related substances. A C18column（4. 6 mm ×150 mm,5 μm） was adopted for quantitative analysis of related substances,with 20 mmol·L- 1potassium dihydrogen phosphate（ p H value was adjusted to 3. 30 with phosphoric acid）- acetonitrile（85 ∶ 15） as mobile phase at a flow rate of 1 m L·min^- 1,and the detection wavelength was set at205 nm. The column temperature was 30 ℃ and the injection volume was 10 μL. Two impurities was confirmed as benzoic acid and phenylacetic acid. Under the optimized chromatographic conditions,the calibration curves of the analytes showed good linearities within the mass concentrations of0. 64- 5. 76 μg·m L^- 1（r = 0. 999 6） for benzoic acid and 0. 65- 5. 82 μg·m L- 1（r = 0. 999 5） for phenylacetic acid. The detection limits for benzoic acid and phenylacetic acid were 1. 3 ng and 1. 6ng,respectively. The average recoveries（ n = 9） were 99. 6% and 99. 0% with relative standard deviations（ RSDs） of 1. 6% and 1. 5%,respectively. The results indicated that HPLC / QTOF- MS method could be effectively used to perform the identifications of related substances in α-ketophenylalanine calcium. The method for quantitative determination of related substances was sensitive,reproducible,accurate and reliable. It could be applied in the analysis of the related substances and the quality control of α-ketophenylalanine calcium in raw material.