HPLC-MS/MS测定盐酸苯乙双胍及片剂中双氰胺的含量

Determination of Dicyandiamide in Phenformin Hydrochloride and Phenformin Hydrochloride Tablets by HPLC-MS/MS

目的建立高效液相色谱-质谱/质谱(HPLC-MS/MS)测定盐酸苯乙双胍及片剂中有关物质双氰胺含量的方法。方法色谱条件:采用Agilent Eclipse XDB-C18色谱柱(4.6mm×150mm,3.5μm),以甲醇-0.1%甲酸溶液(30:70)为流动相;流速:0.5mL.min-1;柱温:30℃;质谱条件:采用大气压化学电离(APCI)源进行正离子检测,选择离子监测(SRM)方式定量分析,双氰胺和内标盐酸苯丙醇胺的监测离子对分别为m/z85→68和m/z152→134。结果 HPLC-MS/MS测定盐酸苯乙双胍中双氰胺含量的线性范围为0.001～10.41μg.mL-1(r=0.9999);加样回收率平均值达98.0%,RSD为1.8%;中间精密度的RSD为5.3%;重复性的RSD为1.9%。结论本法灵敏度高、专属性强、简便、快速、准确,适用于盐酸苯乙双胍及片剂中双氰胺的定量测定。

OBJECTIVE To establish a HPLC-MS/MS method for the determination of dicyandiamide in phenformin hydrochloride and phenformin hydrochloride tablets.METHODS The separation was performed on an Agilent Eclipse XDB-C18 column （4.6 mm×150 mm,3.5 μm） with the mobile phase consisting of methanol-0.1% formic acid solution （30：70）,at a flow rate of 0.5 mL·min-1.Column temperature was 30 ℃.Atmospheric pressure chemical ionization （APCI） source was applied and operated in the positive ion mode in select reaction monitoring （SRM） mode.The fragmentation transitions from precursor to production were m/z 85→68 for dicyandiamide and m/z152→134 for phenylpropanolamine hydrochloride respectively.RESULTS The calibration curve of dicyandiamide was linear in the range from 0.001 to 10.41 μg·mL^-1 （r=0.999 9）.The mean recovery was 98.0% and the RSD was 1.8%.Intermediate precision of RSD was 5.3%.Repeatability of RSD was 1.9%.CONCLUSION This method is sensitive,specific,simple,rapid and accurate,and is suitable for the determination of dicyandiamide in phenformin hydrochloride and phenformin hydrochloride tablets.