開發毛細管電泳方法分析人體血漿中Paliperidone藥物濃度

Determination of Paliperidone in Human Plasma by Capillary Electrophoresis.

劉祥音(Hsiang-Yin Liu)

指導教授 ： 郭錦樺

國立臺灣大學/醫學院/藥學研究所/碩士(2012年)

https://doi.org/10.6342/NTU.2012.10225

摘要

美國食品藥物管理局(US Food and Drug Administration)於2007 年核准paliperidone 做為精神病患急性發作及長期治療之藥物，目前已廣泛被用於精神病患者的治療。Paliperidone 的生體可用率低，藥物吸收易受高脂食物影響。其療效區間範圍狹窄，可能因個體差異而使體內paliperidone 落在療效區間之外，使治療效果不彰或發生副作用，故本研究開發並確效一靈敏的毛細管電泳膠束電動層析
法來分析人體血漿中paliperidone 藥物濃度。本研究利用Oasis® HLB 1 mL (30 mg)Extraction Cartridge 開發固相萃取法進行樣品前處理，並最佳化各項會影響膠束電動層析效力之參數。經固相萃取後樣品回溶的基質組成為10%甲醇及250 mM 磷酸，背景溶液之組成為100 mM 十二烷基硫酸鈉、75 mM 磷酸、12%乙腈及15%四氫呋喃，並使用risperidone 做為內標準品，paliperidone 可在17 分鐘內和血中內生性物質達基線分離。分析物之遷移時間一日內再現性與異日內再現性小於3.09%RSD (n=3)，分析物和內標準品risperidone 的峰面積比值一日內再現性與異日內再現性小於6.03% RSD (n=3)。Paliperidone 校正曲線的線性範圍介於20 ng mL-1到200ng mL-1 之間，涵蓋臨床有效治療濃度範圍，最低偵測濃度為10 ng mL-1，準確度介在93.4%-97.9%之間。研究者針對paliperidone 開發一靈敏的毛細管電泳分析方法除了可檢測病患者血中藥物濃度，或可預測因服用paliperidone 引發外錐體副作用的可能性。本分析方法為第一個應用毛細管電泳分析平臺分析定量人體血中paliperidone 藥物濃度之分析方法，未來有潛力被應用在臨床療劑監測以維護病患用藥安全、預測治療成效以提升治療成功率。

關鍵字

Paliperidone ； 毛細管電泳 ； 膠束電動層析法 ； 療劑監測 ； 血漿

並列摘要

Determination of paliperidone in human plasma by capillary electrophoresis. A simple, accurate and sensitive method is described for the determination of paliperidone in human plasma using risperidone as the internal standard. Paliperidone was extracted from human plasma by Oasis HLB solid phase extraction (SPE) cartridge. The optimized separation is performed in a background electrolyte composed of phosphoric acid (75 mM) containing sodium dodecyl sulfate (100 mM), acetonitrile (12%, v/v), and tetrahydrofuran (15%, v/v). The peaks were detected using a UV detector set at 240 nm, and the total time for one run was about 17 min. Results showed that this analytical method was able to detect paliperidone at concentration of 10 ng/mL (S/N > 3) and the linear range was 20–200 ng mL-1, with the correlation coefficients above 0.99. Method precision and accuracy were tested at 20, 120 and 200 ng mL-1.
Intra- and interday precision of peak area ratio were less than 6.03%; method accuracy was between 93.4% and 97.9%. This is the first analytical method to quantify the concentration of paliperidone in human plasma by capillary electrophoresis. This newly developed method appears to be applicable to therapeutic drug monitoring and clinical research.

並列關鍵字

Paliperidone ； Capillary electrophoresis ； Sweeping-MEKC ； Plasma ； Therapeutic drug monitoring

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