| Objective: To develop a method for the determination of propofol concentration in plasma by using Gas Chromatography-Mass Spectrometry (GC-MS) and to provide scientific analysis for the studies of the pharmacokinetic-pharmacodynemic of propofol. And based on this method, to analyze the differences between target and measured concentration and to evaluate the performance of target controlled infusion (TCI) for propofol on Chinese. Methods: The propofol in plasma was extracted with chloroform-ethyl acetate and was determined by GC-MS. Thymol was used as the internal standard. The GC-MS apparatus (HP-6890GC and HP-5973MS, Hewlett Packard, USA) containing a HP-5(30m×0.25mm×0.25μm film thickness) capillary column was used. Injector inlet (splitless) and detector temperatures were 240°Cand 280℃, respectively. The oven temperature for propofol quantitation was held at 55℃ for 1min, increased at 20℃ ·min-1 to 150℃ and maintained at 150℃ for 3 min, and runtime was 8. 75min. The helium gas flaw-rate was 1ml · min-1 and the column head pressure was 7. 99 p. s. i at 55℃ (1 p. s. i=6. 9kPa). The electron energy was 70eV, MS Source and MS Quad temperatures were 230 ℃ and 150 ℃, respectively. Monitoring ions for the quality and quantitation of propofol and thymol were used as follows: fragment-ion m/z 163 and molecule-ion m/z 178 for propofol, fragment-ion m/z 135 and molecule-ion m/z 150 forthymol. In clinical practice, target-controlled infusion of propofol was administered to Sixty-one ASA I-II scheduled operations of patients (male 26, female 35), aged 42. 82± 12.95 years old weighing 58. 47 ± 8. 98kg. Radial artery was cannulated for blood pressure monitoring and blood sampling. Anesthesia was induced and maintained with propofol and fentanyl. A single constant target plasma propofol concentration was 3μg·ml-1 and Constant infusion time was 1 hour. A loading dose of fentanyl 2μg · kg-1 was given followed by 2μg·kg-1. When the patients were unconscious, intubation was facilitated with vecuronium 0.1mg · kg-1. The TCI system consisted of DellTM InspironTM 8200 computer, Graseby 3500 infusion pump, Stelpump software (Version 1. 07 by JF Coetzee and R Pina), and the pharmacokinetic model and parameters by Tackley et al. Blood samples were obtained before, 2-60min during and 30min after TCI for determination of blood propofol concentration by Gas Chromatography-Mass Spectrometry (GC-MS). Results: The propofol was separated on Chromatography column (HP-5 capillary column) of GC and the oven temperature was programmed. MS was highly selected and sensitive detector. The present method extracted propofol in plasma was using extraction procedure, adjusted to the determination of propofol concentration in plasma by GC-MS. For the extraction procedure, borate buffer was preferred to pH 9. Because excess alkali induces emulsion formation with chloroform making the separation of organic layer and plasma critical. After chloroform-ethyl acetate was added, the mixture should be an inversion mixture. Because the density of chloroform-ethyl acetate is larger than that of plasma. A linear relationship was obtained by an unweighted linear regression analysis between the ratio of the area of ionm/z 163 of propofol to ion m/z 135 of thymol, and the concentration of propofol. The linear range were 0. 25~8.0μg ·ml -1(Y=0. 8457X+0. 1337 R2=0. 9997). This kind of method was high recovery (98-102%) and fine reproducibility (precise<6%). The limit of detection was 10ng · ml-1. Compared with target concentrations, the measured concentrations of propofol were significantly higher during TCI, but lower after TCI. Differences between target and measured concentrations were significant during T1-15 (infusion 2-90min, P<0.05) . During propofol infusion, median performance error (MDPE), median absolute performance error (MDAPE), wobble, and divergence were 30.02%, 31.55%, 21.42%, and - 0. 51%/h, respectively. After infusion, MDPE, MDAPE, wobble, and divergence were - 19.71%, 21.63%, 13.29%, and - 0. 26%/h, respectively. Conclusion:...
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