李岑+王新宇+高敬林+石蕊++趙可新+張立娜+蔣曄

[摘要] 目的 以中空纖維離心超濾（HFCF-UF）技術(shù)為基礎(chǔ)，建立一個(gè)準(zhǔn)確、靈敏、簡(jiǎn)便的分析人血漿中氨茶堿濃度的方法，并應(yīng)用于氨茶堿臨床治療藥物監(jiān)測(cè)。 方法 取500 μL血漿樣品放入U(xiǎn)型超濾管中，再加入200 μL甲醇，渦旋5 min，混勻，將中空纖維剪成15 cm的小段，對(duì)折插入U(xiǎn)型超濾管中，離心力4000 r/min，離心15 min，得可用于進(jìn)樣分析的超濾液；以Diamonsil C18（150 mm×4.6 mm，5 μm）為色譜柱，以甲醇∶10 mmol/L乙酸銨緩沖溶液（20∶80）為流動(dòng)相系統(tǒng)洗脫，流速1.0 mL/min，檢測(cè)波長(zhǎng)為275 nm，進(jìn)樣量為20 μL。 結(jié)果 血漿中氨茶堿濃度在0.528～52.8 μg/mL范圍內(nèi)線性關(guān)系良好（R2 = 0.9972），絕對(duì)回收率范圍是98.1%～101.2%，RSD均小于1.7%。 結(jié)論 該方法操作簡(jiǎn)便，結(jié)果準(zhǔn)確，回收率接近100%，不僅提高了藥物分析人員的工作效率與結(jié)果的準(zhǔn)確性，而且所需樣品量少，能夠滿足生物樣品采集時(shí)患者的耐受性，為氨茶堿的臨床治療藥物監(jiān)測(cè)提供了一個(gè)可靠的分析平臺(tái)，同時(shí)，為進(jìn)一步研究氨茶堿個(gè)體差異、制訂最優(yōu)給藥方案等提供了有效的分析手段。

[關(guān)鍵詞] 氨茶堿；血藥濃度；中空纖維；前處理方法；治療藥物監(jiān)測(cè)

[中圖分類號(hào)] R969.1；R974.3 [文獻(xiàn)標(biāo)識(shí)碼] A [文章編號(hào)] 1673-7210（2017）05（a）-0021-04

Determination of the concentration of aminophylline in human plasma by hollow fiber centrifugal ultrafiltration

LI Cen1 WANG Xinyu2 GAO Jinglin2 SHI Rui1 ZHAO Kexin1 ZHANG Li'na2 JIANG Ye2

1.Department of Pharmacy， CNPC Central Hospital， Heibei Province， Langfang 065000， China； 2.School of Pharmacy， Hebei Medical University， Hebei Province， Shijiazhuang 050017， China

[Abstract] Objective An accurate， sensitive and simple method was developed to determine the concentration of aminophylline （APY） in human plasma based on hollow fiber centrifugal ultrafiltration （HFCF-UF）， and was applied to detect APY of therapeutic drugs monitoring （TDM）. Methods Approximately 500 μL of plasma sample were placed into a U-glass tube， then， adding 200 μL of methanol， the solutions were mixed by vortex. Hollow fibre cut into 15 cm was placed in tube by folding， and ultrafiltrate was obtained for analysis by centrifugation at 4000 r/min for 15 min. The separation was performed on a Diamonsil C18 column （150 mm×4.6 mm， 5 μm） under an isolate elution with a mixture of methanol∶10 mmol ammonium acetate （20∶80， v/v）， the flow rate was 1.0 mL/min， the wavelength was 275 nm and the injection volume was 20 μL. Results APY showed a good linear range in 0.528-52.8 μg/mL （R2 = 0.9972）. The extraction recoveries ranged from 98.1% to 101.2% with RSD less than 1.7%. Conclusion The proposed method is simple， accurate and precise， which not only improves the working efficiency， but also ensures the accuracy of test results. What's more， the method requires a small amount of sample， increasing patient compliance. In general， the novel method applies a feasible way for the monitoring of APY in TDM， furthermore， provides a technique for researching the individual difference of APY， and optimizes individualized dosage regimen.

[Key words] Aminophylline； Plasma drug concentration； Hollow fiber； Preparation method； Therapeutic drugs monitoring