LC-MS/MS法测定产妇乳汁中舒芬太尼的浓度
|
摘要
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%~(-1)00. 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~(-1)96. 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~(-1)9. 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.
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%~(-1)00. 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~(-1)96. 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~(-1)9. 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.
引文
[1]盛夕曼,洪静芳,王维利,等.社区初产妇母乳喂养自我效能调查及影响因素研究[J].中国全科医学,2015,18(2):191-195.
[2]孙冬黎,郑彩虹.妊娠期和哺乳期抗乙肝病毒药物治疗的安全性[J].中国现代应用药学,2017,34(11):1635-1642.
[3]王拢拢,杨锐.哺乳期抗甲状腺药物的选择和应用[J].实用妇产科杂志,2017,33(3):182-184.
[4]Berlin CM,Brigge EJ.Prediction concentrations in human skim milk from plasma protein binding and acid-base characteristics[J].Br J Clin Pharmacol,2013,25:495-503.
[5]谭小平,丁也,郭阳,等.拉莫三嗪在产后早期癫痫女性乳汁中的分泌特点及母乳喂养安全性评价[J].实用药物与临床,2017,20(9):1043-1047.
[6]Niemegeers CJ,Schellekens KH,Van Bever WF,et al.Sufentanil,a very potent and extremely safe intravenous morphine-like compound in mice,rats and dogs.[J].Arzneimittel-Forschung,2014,26(8):1551-1556.
[7]Minkowitz HS.A review of sufentanil and the sufentanil sublingual tablet system for acute moderate to severe pain[J].Pain Manag,2015,5:237-250.
[8]Weldon ST,Perry DF,Cork RC,et al.Detection of pictogram levels ofsufentanil by capillary gas chromatography[J].Anesthesiology,2015,63:684-687.
[9]Boutroy MJ,Bianchetti G,Dubruc C,et al.To nurse when receiving acebutolol:is it dangerous for the neonate?[J].Eur JClin Pharmacol,1986,30(6):737-739.
[10]Schmimmel MS,Eidelman AJ,Wilschanski MA,et al.Toxic effects of atenolol consumed during breast feeding[J].J Pediatr,2016,114:476-478.
[11]王娇,孙佳,赵来刚,等.UPLC-MS/MS测定新生儿和产妇血浆中罗哌卡因和舒芬太尼[J].中国药学杂志,2017,52(01):57-62.
[12]梁李丽.UPLC-MS/MS法测定人血浆中舒芬太尼浓度及舒芬太尼靶控输注系统准确性评估[D].南方医科大学,2011.
[13]曾晓晖.HPLC/MS/MS法测定人血浆中舒芬太尼的血药浓度[C]//广东省药学会.2010年广东省药师周大会论文集.广州:广东省药学会,2011:1.
[14]盛晓燕.HPLC-MS/MS测定舒芬太尼血药浓度及其群体药动学研究[C]//中国药学会.2010施慧达杯第十届全国青年药学工作者最新科研成果交流会论文集.北京:中国药学会,2010:11.
[15]刘维,熊歆,张现化,等.液质联用法检测人血浆中舒芬太尼浓度[J].中国临床药理学杂志,2017,33(9):825-827+831.
[16]曾晓晖,石磊,赵树进,等.LC-MS/MS法测定人血浆中舒芬太尼的血药浓度[J].中国临床药学杂志,2010,19(2):93-96.
[17]王彩云,谷日旭,王玲.GC/MS法测定血液中芬太尼浓度[J].中国卫生检验杂志,2005(8):951.
[18]时捷,车振勇,倪天军,等.高效液相色谱法检测舒芬太尼在硬脊膜外腔分娩镇痛中对新生儿的安全性[J].上海医学,2016,39(10):621-624.
[19]陈凤英,汪凤梅,国强,等.高效液相色谱法测定人乳汁中枸橼酸芬太尼浓度[J].中国药学杂志,2009,44(13):1022-1024.
[20]肖仲祥,王晓燕,郑海燕,等.高效液相色谱法测定乳汁和血浆中的氟比洛芬浓度[J].中国医院药学杂志,2017,37(22):2255-2258.
[21]刘容吉,张乐嘉,付强,等.高效液相色谱法测定人乳汁中羟氯喹浓度[J].临床药物治疗杂志,2016,14(2):23-26.
[22]段世明.舒芬太尼临床药代动力学研究[J].国外医学.麻醉学与复苏分册,1993(3):135-137.
[23]肖彬,张兴安,施冲.舒芬太尼临床药动学研究及应用[J].中国现代应用药学,2008(4):298-301.
[24]于晶晶.药物排入乳汁及婴儿摄入体内的量[J].湖州师范学院学报,2001(6):69-71.
[25]Wen J,Qiao Y,Yang J,et al.UPLC-MS/MS determination of paeoniflorin,naringin,after oral administration of Si-Ni-San decoction[J].J Pharm Biomed Anal,2012,66(6):271-277.
[26]Chen L,Liu L,Zhu W,et al.Comparative pharmacokinetic studies of peimine and peiminine in rat plasma by LC-MS/MSafter oral administration of Fritillaria thunbergii Miq.and Fritillaria thunbergii Miq.-Glycyrrhiza uralensis Fisch.couple extract[J].Pharmazie,2011,66(9):684-689.
[27]Dams R,Huestis MA,Lambert WE,et al.Matrix effect in bio-analysis of illicit drugs with LC-MS/MS:influence of ionizationtype,sample preparation,and bio fluid[J].J Am Soc Mass Spectrom,2003,14(11):1290-1294.
[28]Ferreiro-Vera C,Priego-Capote F,Luque de Castro MD.Comparison of sample preparation approaches for phospholipids profiling in human serum by liquid chromatography-tandem mass spectrometry[J].J Chromatogr A,2012,1240(11):21-28.
[29]Atkinson HC,Begg EJ,Darlow BA.Drugs in human milk1 Clinical pharmacokinetic considerations[J].Clin Pharmacokinetic,1988,14:217-240.
[2]孙冬黎,郑彩虹.妊娠期和哺乳期抗乙肝病毒药物治疗的安全性[J].中国现代应用药学,2017,34(11):1635-1642.
[3]王拢拢,杨锐.哺乳期抗甲状腺药物的选择和应用[J].实用妇产科杂志,2017,33(3):182-184.
[4]Berlin CM,Brigge EJ.Prediction concentrations in human skim milk from plasma protein binding and acid-base characteristics[J].Br J Clin Pharmacol,2013,25:495-503.
[5]谭小平,丁也,郭阳,等.拉莫三嗪在产后早期癫痫女性乳汁中的分泌特点及母乳喂养安全性评价[J].实用药物与临床,2017,20(9):1043-1047.
[6]Niemegeers CJ,Schellekens KH,Van Bever WF,et al.Sufentanil,a very potent and extremely safe intravenous morphine-like compound in mice,rats and dogs.[J].Arzneimittel-Forschung,2014,26(8):1551-1556.
[7]Minkowitz HS.A review of sufentanil and the sufentanil sublingual tablet system for acute moderate to severe pain[J].Pain Manag,2015,5:237-250.
[8]Weldon ST,Perry DF,Cork RC,et al.Detection of pictogram levels ofsufentanil by capillary gas chromatography[J].Anesthesiology,2015,63:684-687.
[9]Boutroy MJ,Bianchetti G,Dubruc C,et al.To nurse when receiving acebutolol:is it dangerous for the neonate?[J].Eur JClin Pharmacol,1986,30(6):737-739.
[10]Schmimmel MS,Eidelman AJ,Wilschanski MA,et al.Toxic effects of atenolol consumed during breast feeding[J].J Pediatr,2016,114:476-478.
[11]王娇,孙佳,赵来刚,等.UPLC-MS/MS测定新生儿和产妇血浆中罗哌卡因和舒芬太尼[J].中国药学杂志,2017,52(01):57-62.
[12]梁李丽.UPLC-MS/MS法测定人血浆中舒芬太尼浓度及舒芬太尼靶控输注系统准确性评估[D].南方医科大学,2011.
[13]曾晓晖.HPLC/MS/MS法测定人血浆中舒芬太尼的血药浓度[C]//广东省药学会.2010年广东省药师周大会论文集.广州:广东省药学会,2011:1.
[14]盛晓燕.HPLC-MS/MS测定舒芬太尼血药浓度及其群体药动学研究[C]//中国药学会.2010施慧达杯第十届全国青年药学工作者最新科研成果交流会论文集.北京:中国药学会,2010:11.
[15]刘维,熊歆,张现化,等.液质联用法检测人血浆中舒芬太尼浓度[J].中国临床药理学杂志,2017,33(9):825-827+831.
[16]曾晓晖,石磊,赵树进,等.LC-MS/MS法测定人血浆中舒芬太尼的血药浓度[J].中国临床药学杂志,2010,19(2):93-96.
[17]王彩云,谷日旭,王玲.GC/MS法测定血液中芬太尼浓度[J].中国卫生检验杂志,2005(8):951.
[18]时捷,车振勇,倪天军,等.高效液相色谱法检测舒芬太尼在硬脊膜外腔分娩镇痛中对新生儿的安全性[J].上海医学,2016,39(10):621-624.
[19]陈凤英,汪凤梅,国强,等.高效液相色谱法测定人乳汁中枸橼酸芬太尼浓度[J].中国药学杂志,2009,44(13):1022-1024.
[20]肖仲祥,王晓燕,郑海燕,等.高效液相色谱法测定乳汁和血浆中的氟比洛芬浓度[J].中国医院药学杂志,2017,37(22):2255-2258.
[21]刘容吉,张乐嘉,付强,等.高效液相色谱法测定人乳汁中羟氯喹浓度[J].临床药物治疗杂志,2016,14(2):23-26.
[22]段世明.舒芬太尼临床药代动力学研究[J].国外医学.麻醉学与复苏分册,1993(3):135-137.
[23]肖彬,张兴安,施冲.舒芬太尼临床药动学研究及应用[J].中国现代应用药学,2008(4):298-301.
[24]于晶晶.药物排入乳汁及婴儿摄入体内的量[J].湖州师范学院学报,2001(6):69-71.
[25]Wen J,Qiao Y,Yang J,et al.UPLC-MS/MS determination of paeoniflorin,naringin,after oral administration of Si-Ni-San decoction[J].J Pharm Biomed Anal,2012,66(6):271-277.
[26]Chen L,Liu L,Zhu W,et al.Comparative pharmacokinetic studies of peimine and peiminine in rat plasma by LC-MS/MSafter oral administration of Fritillaria thunbergii Miq.and Fritillaria thunbergii Miq.-Glycyrrhiza uralensis Fisch.couple extract[J].Pharmazie,2011,66(9):684-689.
[27]Dams R,Huestis MA,Lambert WE,et al.Matrix effect in bio-analysis of illicit drugs with LC-MS/MS:influence of ionizationtype,sample preparation,and bio fluid[J].J Am Soc Mass Spectrom,2003,14(11):1290-1294.
[28]Ferreiro-Vera C,Priego-Capote F,Luque de Castro MD.Comparison of sample preparation approaches for phospholipids profiling in human serum by liquid chromatography-tandem mass spectrometry[J].J Chromatogr A,2012,1240(11):21-28.
[29]Atkinson HC,Begg EJ,Darlow BA.Drugs in human milk1 Clinical pharmacokinetic considerations[J].Clin Pharmacokinetic,1988,14:217-240.