[Determination of tramadol and its active metabolite O-desmethyltramadol in plasma and amniotic fluid using LC/MS/MS].
OBJECTIVE
To determinate tramadol and O-desmethyltramadol in human plasma and amniotic fluid by LC/MS/MS, and distribution of tramadol and O-desmethyltramadol in maternity and fetus were studied.


METHODS
Samples containing tramadol, O-desmethyltramadol and diphenhydramine (internal standard, IS ) were extracted using liquid-liquid extraction, followed by liquid chromatographic separation and on-line MS/MS using atmospheric pressure chemical ionization as an interface detection. The analytes were detected in the selected reaction monitoring mode.


RESULTS
The calibration curves for tramadol and O-desmethytramadol in plasma and amniotic fluid were linear in the range from 8.0 to 800.0 microg x L(-1) (plasma) and 1.0 to 400.0 microg x L(-1) (amniotic fluid). The method was applied to the measurement of tramadol and O-desmethytramadol concentrations in maternal vein, umbilical vein, umbilical artery and amniotic fluid. Following intramuscular pre-operative administration 1.5 mg x kg(-1) doses of tramadol to parturients, plasma concentrations of tramadol were significantly higher than those in amniotic fluid. The concentrations of O-desmethyltramadol in plasma were lower, and were not detected in amniotic fluid.


CONCLUSIONS
The method is shown to be accurate, robust and convenient, and suitable for clinical pharmacokinetics studies of tramadol and O-desmethyltramadol.
Zhao
Li-mei
LM
Laboratory of Clinical Pharmacology, China Medical University No. 2 Hospital, Shenyang 110004, China.
Chen
Xiao-yan
XY
Cui
Jian-jun
JJ
Sunita
Maleku
M
Zhong
Da-fang
DF
D000653:Amniotic Fluid / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005333:Fetus; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D011247:Pregnancy; D021241:Spectrometry, Mass, Electrospray Ionization; D014147:Tramadol / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D014469:Umbilical Arteries / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism*
C080580:O-demethyltramadol; D014147:Tramadol