LC-MS/MS法测定产妇乳汁中舒芬太尼的浓度

Determination of the sufentanil in parturient women breast milk by LC-MS/MS

目的:测定产妇经静脉输注泵给予舒芬太尼的镇痛期间和镇痛结束后不同时间点的乳汁药物浓度,为临床产后镇痛过程中的母乳喂养安全性研究提供测定方法与参考。方法:采用梯度洗脱,ESI离子源,使用正离子模式,多反应离子监测(MRM),液-液萃取法,加入正己烷和乙酸乙酯(1:9,V/V)提取。结果:在3. 2-400 pg·mL^(-1)的线性关系良好(R2=0. 998),定量下限为3. 2 pg·mL^(-1),提取回收率在83. 1%^(-1)00. 7%。样品测得的最低浓度(停药22 h)为4. 75 pg·mL^(-1),最高浓度(用药31 h)为196. 74 pg·mL^(-1)。持续镇痛24 h后,药物浓度在27. 19^(-1)96. 74 pg·mL^(-1)之间;停药后2-20 h,乳汁中的药物浓度在7. 88-21. 58 pg·mL^(-1)之间,停药超过20 h的药物浓度在4. 75^(-1)9. 22 pg·mL^(-1)之间。结论:建立LC-MS/MS法检测,灵敏度高、速度快、操作简单、抗干扰能力强,可准确测定乳汁中微量的舒芬太尼药物浓度。

Objective: Determination of sufentanil in parturient women breast milk in different time points during the administration of the analgesic drug sufentanil via the IV infusion pump in order to determine whether the breastfeeding after clinical anesthetic or analgesic administration has an effect on the infant and provide a method for the further study.Methods: Linear gradient was applied and ESI source was operated in positive ion mode. Liquid-liquid extraction was used with n-hexane ethyl acetate( 1: 9,V/V).Results: Over the concentration range of 3. 2-400 pg · mL^-1 was linear,and the correlation coefficient( r2) were greater than 0. 998. The lower limit of quantification( LLOQ) was 3. 2 pg·mL^-1. The extraction recovery of sufentanil was more than 83. 1%-100. 7%. The lowest concentration( 22 h after drug withdrawal) was 4. 75 pg· mL^-1,and the highest concentration( 31 h after analgesia)was 196. 74 pg · mL^-1. After continuous analgesia for more than 24 h,the drug concentration was27. 19-196. 74 pg · mL^-1. The drug concentration( 2-20 h after drug withdrawal) in the milk was between 7. 88-21. 58 pg ·mL^-1 and it was 4. 75-19. 22 pg · mL^-1 when drug withdrawal for more than 20 h.Conclusion: The method was sensitive,rapid and accurate,which can be applied to analysis the low concentration of sufentanil in human breast milk.