HPLC-MS/MS测定盐酸苯乙双胍及片剂中双氰胺的含量

 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(4.6 mm×150 mm，3.5 μm)，以甲醇-0.1%甲酸溶液(30∶70) 为流动相；流速：0.5 mL·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0.001～10.41 μg·mL-1 (r=0.999 9)；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。

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

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.