The studying of high throughput screening of the common controlled drugs and novel abused drugs in urine by ultra high-performance liquid chromatography/tandem mass spectrometry
本計畫主要是利用極致高效能液相層析法結合串聯質譜術，於高通量快速篩檢尿液中常見第一~第四級管制藥物與新興濫用藥物分析方法之開發與比較。研究中選定常見的第一~第四級管制藥品包括安非他命、甲基安非他命、MDA、MDMA、MDEA、嗎啡、海洛英、古柯鹼及其代謝物苯甲醯基愛哥寧、可待因、美沙東、愷他命及其代謝物去甲基愷他命、氟硝西泮(FM2)、阿普唑他、二氮平、勞拉西泮、硝甲西泮、硝西泮、佐配眠、三唑他、Δ8-四氫大麻酚、Δ9-四氫大麻酚及大麻代謝物四氫大麻酚-9-甲酸，以及新興濫用藥物4-甲基甲基卡西酮(喵喵)與氯安非他命等二十六種藥物為主要分析物。計畫中分別針對極致高效能液相層析法及串聯質譜法進行系統性最佳化探討，並針對靈敏度和準確度與文獻進行比較。計畫中將針對使用填充次二微米(sub-2 μm)以及核殼技術(core-shell)兩種不同填充材質的極致高效能液相層析管柱，進行液相層析分離條件中動相組成與分離沖提梯度，對於二十六種分析物之分離效果進行最佳化之探討。計畫中採用串聯質譜技術中高選擇性反應偵測模式(highly selected reaction monitoring，h-SRM)，進行二十六種分析物之偵測，且針對不同離子化效率進行最優化之討論。方法確效方面，研究將針對極致高效能液相層析法結合串聯質譜術分析尿液檢體中常見第一~第四級管制藥物與新興濫用藥物之線性範圍、最低定量極限、偵測極限、再現性、準確性與回收率進行探討。最後將此分析方法對於真實尿液檢體樣品進行高通量之分析，並評估此方法做為濫用藥物尿液篩檢技術之參考。This project will investigate the feasibility of applying ultra high-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) for simultanous determination of 24 common controlled drugs and 2 novel abused drug in urine. The target analytes are including amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy- methamphetamine (MDMA), 3,4- methylenedioxyethylamphetamine (MDEA), chloroamphetamine, mephedrone, morphine, heroin, cocaine, benzoylecgonine, codeine, methadone, ketamine, norketamine, flunitrazepam, alprazolam, diazepam, lorazepam, nimetazepam, nitrazepam, triazolam, zolpidem, Δ8-THC, Δ9-THC, 11-nor-Δ9-tetrahydrocannabinol- 9-carboxylic acid. Two UPLC columns, packed with sub-2 μm material and core-shell material,will be tested in this study for rapid separation of 26 analytes. The chromatographic conditions including compositions of mobile phase and separation gradient will be systematic optimized. The highly selected reaction monitoring (h-SRM) will be utilized to determine 26 analytes, and the mass spectrometric conditions will be optimized. The validation of proposed method including linear detection ranges, limit of quantitation, limit of detection and reproducibility will be systematic evaluated. The feasibility of applying the proposed method to analyze the trace controlled drugs in real urine samples was also examined
