摘要
目的建立高效液相色谱串联质谱法（HPLC-MS／MS）测定人血浆及尿液中二甲啡烷的浓度。方法以重蒸乙醚为萃取剂，采用Ultimate C18（50mm×4．6mm，5μm）色谱柱，流动相为甲醇-水-甲酸=75：25：0．05，流速为0．2mL／min。采用正离子模式，ESI离子源，MRM模式检测，以利多卡因为内标定量，二甲啡烷和内标的检测离子对质荷比分别为（m／z）256．4—155．3和（m／z）235．4—86．1。结果二甲啡烷血药浓度在0．025～5．0ng／mL范围内线性关系良好（r=0．9957），最低定量限为0．025ng／mL；尿药浓度在0．1～20．0ng／mL范围内线性关系良好（r=0．9983），最低定量限为0．1ng／mL。血浆方法回收率为103．38％～106．88oA；尿液方法回收率为90．05％～101．40％。血药浓度日内、日间精密度相对标准偏差（RsD）分别小于5．92％及5．70％，尿药浓度日内、日间精密度RSD分别小于10．35％及8．80％。结论本研究建立的方法准确、灵敏、可靠，可用于二甲啡烷的血药浓度和尿药浓度的测定及其药代动力学研究。
Objective To develop a sensitive and reproducible HPLC-MS/MS method for analyzing dimemorfan in human plasma and urine. Methods Dimemorfan was extracted from plasma and urine by redistilled ether, with lidocaine serving as the internal standard （IS）. The analysis was performed on a column of ultimate C18 （50 mm×4.6 mm, 5 μm） with the mobile phase consisting of methyl alcohol-water-formic acid=75 ： 25 ： 0.05 at a flow rate of 0. 2 mL/min. Dimemorfan was detected by API 3000 mass spectrometer, with multiple reaction monitoring after protonated with ESI in positive electron ionization mode. The ion pairs being detected were （m/z） 256.4→155.3 （dimemorfan） and 235.4→86. 1 （lidocaine）, respectively. Results The regression equation for dimemorfan showed excellent linearity （r= 0. 995 7） from 0. 025 to 5.0 ng/mL of plasma with detecting limitation of 0. 025 ng/mL and perfect linearity （r= 0. 998 3） from 0. 1 to 20. 0 ng/mL of urine with detecting limitation of 0.1 ng/mL. The method recoveries of dimemorfan in plasma and urine were ranging from 103. 38% to 106.88% and 90.05% to 101.40%, respectively. The maximum intra-day and inter-day relative standard deviations （RSD） of concentration of dimemorfan were 5.92% and 5.70% （for plasma）, 10.35% and 8.80% （for urine）, respectively. Conclusion This new method was validated to be accurate and sensitive to determinate the concentration of dimemorfan in plasma and urine samples, and can be applied for pharmacokinetic studies of dimemorfan.
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2014年第3期497-501,共5页
Journal of Sichuan University(Medical Sciences)
