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目的鉴定肌酐-三氯氧磷缩合法生产的磷酸肌酸钠中一个新发现的杂质(1),并建立其含量测定方法。方法通过核磁共振、ESI高分辨质谱、X单晶衍射等光谱学方法解析该杂质1的结构;采用反相高效液相色谱法测定含量,使用C_(18)色谱柱,以乙腈-质量分数为0.2%的磷酸二氢钠水溶液(含质量分数为0.1%的四丁基氢氧化铵,磷酸或氨试液调节p H值至6.6)(体积比为20∶80)为流动相,检测波长:210 nm。结果杂质1鉴定为具焦磷酰结构的新化合物。反相高效液相色谱法的线性为0.25~100 mg·L~(-1);加样回收率,在磷酸肌酸钠粗品测定中为99.8%(RSD=1.1%,n=6),在精制品测定中为98.6%(RSD=1.6%,n=6)。结论对化学合成法来源的磷酸肌酸钠,可以用HPLC法来测定其中杂质1的含量。
OBJECTIVE: To identify a newly discovered impurity in sodium creatine phosphate (1) produced by the creatinine-phosphorus oxychloride condensation method and to establish a method for its determination. Methods The structure of impurity 1 was analyzed by nuclear magnetic resonance, ESI high resolution mass spectrometry and X single crystal diffraction. The content of impurity 1 was determined by reversed-phase high performance liquid chromatography (HPLC) with C 18 column, 0.2% sodium dihydrogen phosphate aqueous solution (containing tetrabutylammonium hydroxide 0.1%, pH adjusted to pH 6.6 with phosphoric acid or ammonia solution) (20:80 by volume) as mobile phase, detection wavelength: 210 nm . Results Impurity 1 was identified as a new compound with pyrophosphoryl structure. The linearity of RP-HPLC was 0.25-100 mg · L -1. The recovery rate was 99.8% (RSD = 1.1%, n = 6) 98.6% of the final product (RSD = 1.6%, n = 6). Conclusion For the chemical synthesis of sodium creatine phosphate, HPLC method can be used to determine the content of impurity 1.