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余勤, 向瑾, 石玲子, 等. 正相HPLC-MS/MS测定人血浆中多奈哌齐对映体浓度[J]. 四川大学学报(医学版), 2012, 43(5): 779-781,785.
引用本文: 余勤, 向瑾, 石玲子, 等. 正相HPLC-MS/MS测定人血浆中多奈哌齐对映体浓度[J]. 四川大学学报(医学版), 2012, 43(5): 779-781,785.
YU Qin, XIANG Jin, SHI Ling-zi, et al. Determination of Donepezil Enantiomer in Human Plasma by Normal-HPLC-MS/MS[J]. Journal of Sichuan University (Medical Sciences), 2012, 43(5): 779-781,785.
Citation: YU Qin, XIANG Jin, SHI Ling-zi, et al. Determination of Donepezil Enantiomer in Human Plasma by Normal-HPLC-MS/MS[J]. Journal of Sichuan University (Medical Sciences), 2012, 43(5): 779-781,785.

正相HPLC-MS/MS测定人血浆中多奈哌齐对映体浓度

Determination of Donepezil Enantiomer in Human Plasma by Normal-HPLC-MS/MS

  • 摘要: 目的 建立正相高效液相色谱-串联质谱(HPLC-MS/MS)法测定人血浆中多奈哌齐(DN)对映体的方法,并进行方法学验证。 方法 采用正己烷:异丙醇(98:2,V/V)作为萃取剂进行样品浓集,选用CHIRALCEL OJ-H手性柱(250 mm×4.6 mm,5 μm)作分析柱,流动相为正己烷:正丙醇:二乙胺=60:40:0.1(V:V:V),流速为0.5 mL/min,柱温为38℃。以多反应监测(MRM)方式进行定量检测,利多卡因为内标,按内标法定量。 结果 左旋DN(S-DN)、右旋DN(R-DN)对映体的保留时间分别为15.56和18.41 min。S-DN的线性范围为0.051~7.596 ng/mL,R-DN的线性范围为0.049~7.404 ng/mL,线性良好(r>0.99)。S-DN和R-DN的方法回收率分别为95.10%~103.70%、93.58%~98.00%;预处理回收率分别为58.42%~61.08%、53.24%~61.87%;日内精密度(RSD)分别为8.35%~11.28%、6.78%~11.58%;日间RSD分别为5.82%~9.02%、6.87%~9.19%。 结论 建立的正相HPLC-MS/MS测定人血浆多奈哌齐对映体血药浓度具有快速、简便、灵敏、准确等优点,适用于多奈哌齐对映体的人体药动学研究。

     

    Abstract: Objective To develop and validate a normal phase HPLC-MS/MS method for the determination of donepezil enantiomer in human plasma. Methods Donepezil was extracted from plasma by n-hexane:isopropanol (98:2,V/V) with lidocaine serving as an internal standard. The analytes went through the column of CHIRALCEL OJ-H (250 mm×4.6 mm, 5 μm) with mobile phase n-hexane:n-propanol:diethylamine (60:40:0.1,V/V/V). Donepezil enantiomer was determined by API 3000 in MRM mode. Results The retention time of S-DN and R-DN were 15.56 min and 18.41 min, respectively. The calibration curves were linear in a range from 0.051 to 7.596 ng/mL for S-DN, and from 0.049 to 7.404 ng/mL for R-DN, respectively, both with more than 0.99 correlation coefficients. The relative recovery were 95.10%-103.70% for S-DN and 93.58%-98.00% for R-DN, respectively; the pretreatment recovery were 58.42%-61.08% for S-DN and 53.24%-61.87% for R-DN, respectively;; the within-day RSD ranged from 8.35% to 11.28% for S-DN and from 6.78% to 11.58% for R-DN, respectively; the between-day RSD ranged from 5.82% to 9.02% for S-DN and from 6.87% to 9.19% for R-DN, respectively. Conclusion This normal phase HPLC-MS/MS method is simple, rapid, sensitive and accurate for the determination of donepezil enantiomer in human plasma and is suitable for pharmacokinetic studies of donepezil enantiomers.

     

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