丙戊酸及其代謝物的量測方法及其系統METHOD AND SYSTEM FOR MEASURING VALPROIC ACID AND METABOLIC PRODUCT THEREOF

專利類型

發明

專利國別 (專利申請國家)

中華民國

專利申請案號

102129354

專利證號

I 532992

專利獲證名稱

丙戊酸及其代謝物的量測方法及其系統METHOD AND SYSTEM FOR MEASURING VALPROIC ACID AND METABOLIC PRODUCT THEREOF

專利所屬機關 (申請機關)

高雄醫學大學

獲證日期

2016/05/11

技術說明

丙戊酸(valproic acid)為臨床上常用的小分子脂肪酸藥物，廣泛用來治療各類癲癇症和做為情緒穩定用藥，神經醫學常使用此藥物預防神經退化性疾病和做為保護神經系統功用。近年來，癌症研究中發現，valproic acid抑制癌細胞的增生做為治療癌症的新用途。臨床治療運用上，劑量不當造成副作用症產生，包含肝衰竭、胎兒畸形、小兒胰臟炎與高氨血症。文獻中證實valproic acid增加細胞氧化壓力和細胞毒性，與發生臨床副作用症現象，以valproic acid進行治療須進行藥物監控。本技術為搭配基質輔助雷射脫附離子化飛行時間式質譜儀(matrix-assisted laser desorption ionization time-of-flight mass spectrometry; MALDI-TOF MS)建立一套快速有效分析血液中valproic acid以及其毒性代謝物4-ene VPA方法。本技術將檢體經微量溶媒萃取後進行化學衍生反應並進行定量，應用於valproic acid血中濃度監測以及代謝物4-ene VPA監測。結果顯示此技術對valproic acid以及4-ene VPA具有良好線性關係，valproic acid血液定量範圍為10-1000 μM，偵測極限(LOD) 為2 μM，毒性代謝物4-ene VPA血液定量範圍為5-500 μM，偵測極限(LOD)為1 μM，決定系數(coefficient of determination，R2) ≥0.999，相對標準偏差(relative standard deviation，RSD) <5.73%。本技術不但可應用於臨床病患藥物血中濃度定量，也可同時監測血中肝毒性代謝物含量，並且應用在藥品品質管理(quality control)與藥品純度上，結果顯示本技術具有高度準確性和精準度。 Valproic acid(VPA) is wildly used as mood stabilizer, epilepsy treatment and mania prevention. VPA went to a stunning efficiency to ease neurodegeneration syndrome and have potential neuroprotection effect in many research. Furthermore, VPA suppress tumor cell proliferation and may be tend to be treat in cancer because of the cell selectivity. But the drug is usually connected with toxic and teratogenicity. In clinical use of VPA, the dosage and plasma level shall be monitoring in order to avoid drug interaction, liver failure and teratology. The result of this technique, quantitative range for VPA is 10-1000 μM, its toxic metabolite 4-ene VPA is 5-500 μM, the limit of detection are 2 and 1 μM, respectively. Without complicated pretreatment and extraction, it needs just 50 minutes and 20 μL patient blood sample, showing a great linearity, accuracy and precision. Besides, this method could be applied to sample quality control level in pharmacy industry.

備註

連絡單位 (專責單位/部門名稱)

智財保護與科技管理組

連絡電話

07-3138030

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