以氣相層析質譜法分析減肥類中藥製劑摻加西藥成分之研究   全文下載

GC/MS Analysis on Anorectics Adulterated in Traditional Chinese Medicines

Amphetamine, methamphetamine, phentermine, phenylpropanolamine, mazindol, methylphenidate, clobenzorex,fenfluramine, diethylpropion等成分因具抑制食慾作用，被用於減肥瘦身，惟恐被違法摻入減肥類中藥製劑中，遂配製摻加上述成分於防風通聖散模擬中藥檢體，以氣相層析質譜分析法探討同時定性、定量該9種成分及經常檢出之caffeine 及diazepam 等共11 種西藥成分。本研究係以HP5973 氣相層析質譜儀搭配HP6890 GC、HP MSD ChemStation，數據處理軟體及PMW-Tox2 、Wiley 275 及本局自建電腦質譜資料圖庫（NLFD3）等電腦質譜資料圖庫套裝軟體等裝備。毛細氣相層析管為HP-5MS，30M，以70eV離子電能作電子撞擊式（EI mode）分析，由70°C起始溫度維持2 分鐘，再以每分鐘10°C之升溫速率，直到280°C並維持5 分鐘，所得各離子峰全質譜圖（TIC），與上述電腦質譜資料圖庫比對結果均能順利檢出添加之西藥成分，契合度亦均在85%以上。為定量上述11 種成分，配製五種不同濃度之系列對照標準品混合溶液，以dextromethorphan HBr作為內部標準品，以上述分析條件進行選擇離子裂片監控掃描法（selected ions monitor, SIM mode）進行定量分析，製作各檢測成分之檢量線，結果各成分之線性關係γ 值均介於0.9967~0.9999之間。為探討本分析法再現性而進行同日內、異日間之測試，其相對標準偏差值分別介於3.48%~5.52% 及3.07%~6.66% 之間，再現性尚可接受。以上述檢量線定量四件減肥類製劑摻加西藥成分之檢體，結果檢體一含mazindol 0.44 mg／tablet；檢體二含clobenzorex 24.35 mg／cap 、caffeine 1.06 mg／cap 及diazepam 0.54 mg／cap ；檢體三含phentermine 28.42 mg／cap ；檢體四含phentermine 27.33 mg／包及caffeine 11.75 mg／包。"

A gas chromatography/mass spectrometry analytic method was developed for simultaneously identifying and quantitating anorectics synthetic drugs illegally adulterated in traditional Chinese medicines (TCM). A model sample of TCM (Farng-Feng-Tong-Shewg-Saan防 風通聖散濃縮散) was spiked with 11 kinds of synthetic drugs: amphetamine, methamphetamine, methylphenidate, clobenzorex, phentermine, fenfluramine, phenylpropanolamine, caffeine, mazindol, diazepam, diethylpropion. The sample was extracted with methanol. The GC/MS conditions were as follows: initial temperature 70°C, holding 2 mins., ramping rate was 10°C/min by linear, final temperature 280°C, holding 5 mins. The samples were scanned by HP5973 GC/MSD with a quadrupole mass filter in an electron impact mode (70eV), and a total ion current (TIC) chromatogram was obtained with multiple peaks. Comparison was made of the mass chromatograms and retention time of each peak with a created library. The matching quality of each synthetic drug spiked in TCM was not less than 85%. The retention time of each ingredient was consisted with the data created in the library. In quantitative analysis, this method with selected ion monitoring (SIM) analysis was performed. Dextromethophan HBr (50 μg/mL) was used as internal standard. Excellent calibration curves of each analytic compounds had ploted, and correlation coefficients were between 0.9967 and 0.9999. The RSD of interday and intraday studies was between 3.48~5.52% and 3.07~6.66%. The results showed that the established method is quite suitable for determination of anorectics adulterated in TCM samples. By this method, the following was found: 0.44 mg/tab of mazindol in high-fibrous food tablets; 24.35 mg/cap of clobenzorex, 1.06 mg/cap of caffeine, and 0.54 mg/cap of diazepam in herbal capsules; 28.42 mg/cap of phentermine in slimming capsules; 27.33 mg/pack of phentermine and 11.75 mg/sachet of caffeine in TCM dispensing packs. Amphetamine, methamphetamine, phentermine, phenylpropanolamine, mazindol, methylphenidate, clobenzorex,fenfluramine, diethylpropion等成分因具抑制食慾作用，被用於減肥瘦身，惟恐被違法摻入減肥類中藥製劑中，遂配製摻加上述成分於防風通聖散模擬中藥檢體，以氣相層析質譜分析法探討同時定性、定量該9種成分及經常檢出之caffeine 及diazepam 等共11 種西藥成分。本研究係以HP5973 氣相層析質譜儀搭配HP6890 GC、HP MSD ChemStation，數據處理軟體及PMW-Tox2 、Wiley 275 及本局自建電腦質譜資料圖庫（NLFD3）等電腦質譜資料圖庫套裝軟體等裝備。毛細氣相層析管為HP-5MS，30M，以70eV離子電能作電子撞擊式（EI mode）分析，由70°C起始溫度維持2 分鐘，再以每分鐘10°C之升溫速率，直到280°C並維持5 分鐘，所得各離子峰全質譜圖（TIC），與上述電腦質譜資料圖庫比對結果均能順利檢出添加之西藥成分，契合度亦均在85%以上。為定量上述11 種成分，配製五種不同濃度之系列對照標準品混合溶液，以dextromethorphan HBr作為內部標準品，以上述分析條件進行選擇離子裂片監控掃描法（selected ions monitor, SIM mode）進行定量分析，製作各檢測成分之檢量線，結果各成分之線性關係γ 值均介於0.9967～0.9999之間。為探討本分析法再現性而進行同日內、異日間之測試，其相對標準偏差值分別介於3.48%～5.52% 及3.07%～6.66% 之間，再現性尚可接受。以上述檢量線定量四件減肥類製劑摻加西藥成分之檢體，結果檢體一含mazindol 0.44 mg／tablet；檢體二含clobenzorex 24.35 mg／cap 、caffeine 1.06 mg／cap 及diazepam 0.54 mg／cap ；檢體三含phentermine 28.42 mg／cap ；檢體四含phentermine 27.33 mg／包及caffeine 11.75 mg／包。