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Objective: in human plasma sufentanil concentration was measured using liquid chromatography tandem mass spectrometry method to calculate the pharmacokinetic parameters of sufentanil and analysis of pharmacokinetic characteristics. Methods: elective heart surgery patients 16 cases (10 male and 6 female), ASA II or class III, age 34 to 61 years, weight 48 to 80kg. According to the type of disease is divided into two groups: group I (valvular disease group) patients (6 males and 2 females cases); group II (CHD group) in 8 cases (4 males and 4 females). Preoperative history of mental neuropathy, without uncontrolled high blood pressure (BP ≧ 160/100mmHg,), not long-term use of opioids or antipsychotic drugs, body mass index, heart, liver and kidney function is normal. All patients underwent 30 minutes before the intramuscular injection of scopolamine alkali 0.003 to of 0.006mg kg -1 , morphine 0.1 ~ 0.2 mg · kg -1 . Monitoring of blood pressure, heart rate, ECG and pulse oximetry saturation in the patient after the burglary. Open right upper extremity intravenous infusion of sodium lactate Ringer's solution, parallel to the left radial artery for invasive blood pressure monitoring. Mask inhaling pure oxygen. Anesthesia was induced with midazolam 0.05 to 0.1 mg · kg -1 , relying on etomidate 0.2 to 0.3mg · kg -1 , vecuronium 0.1 ~ 0.2 mg · kg -1 , sufentanil 5 ug kg -1 . 3 ~ 5min after intubation, a parallel mechanical ventilation. Do central venous puncture to monitor central venous pressure. Surgery using propofol, vecuronium and isoflurane anesthesia was maintained. In the intravenous sufentanil 1,3,5,10,20,30,60,120,180,240 of 360min left radial artery blood 3ml, placed in heparinized glass test tubes, centrifuged for 10 min (3000r · the min -1 ), precision drawing 1 ml of plasma, -80 ° C low temperature until tested. Specimens plasma 200 ul, within standard were added, mixed, and then acetonitrile was added to 400 ul mixture was vortex mixed 1min, placed for 5 min, centrifuged 10min (15000r · min -1 ), the supernatant was 200 ul into a vial injection volume was 50 ul. LC-MS/MS conditions: column Agilent XDB Eclipse C18 (150 × 4.6 mm, 5μm), mobile phase of 10 mM ammonium acetate (pH 3.0) / acetonitrile = 15/85; flow for 1mL/min. API3000 APCI ion source in positive ion mode, the ion source temperature of 500 ° C, discharge current 3uA. Ion acquisition mode for multiple reaction monitoring (MRM) mode. Ion sufentanil m / z 387.2/238.1, fentanyl (internal standard), m / z 337.2/188.5. Results: 1, valvular disease group: The pharmacokinetics of sufentanil in line with an open three-compartment model plasma concentration time curve of the available three-exponential function: Cp (t) = 24.84e 0.5260t 5.3774e -0.0523t ?? 0.1602e -0.0017t its pharmacokinetic parameters see table 4. A single intravenous injection of sufentanil 5 ug kg -1 , after 1 min average plasma concentration of sufentanil immediately reached 20.8ng ml -1 . 1,5 patients had a small peak at 3 to 5 min after administration, and then continued to decline. 30 minutes after the administration, the plasma concentration of sufentanil decreased by 94.1%. Administered after 60min, 97.5% in the plasma is removed. Turn for the better when sufentanil plasma concentration ratio decreased by 70.6% before turning. 1 patient 4h after administration of the second peak, and then continued to decline. 6 h after administration of sufentanil plasma concentration decreased to 0.05ng · ml -1 , sufentanil breathing does not produce inhibition. The majority of patients after restoration of spontaneous breathing. 2, the group of congenital heart disease: the pharmacokinetics of sufentanil in line with an open three-compartment model of plasma concentration time curve can be expressed in three-exponential function: Cp (t) = 12.79e -0.4571t 3.3295e -0.0462t 0.3999e -0.0048t its pharmacokinetic parameters see table 4. A single intravenous injection of sufentanil 5 ug kg -1 , mean plasma concentration of sufentanil immediately reached after 1 min 11.8ng · ml -1 . 5 ~ 10 minutes after administration of 10, 14 patients had a small peak, and then continued to decline. 30 minutes after the administration, the plasma concentration of sufentanil decreased by 90.4%. Administered after 60min, 95.6% in the plasma is removed. Turn for the better after sufentanil plasma concentration dropped dramatically before turning down 52.0%. 6 h after administration of sufentanil plasma concentration decreased to 0.07ng · ml -1 . The two sets of pharmacokinetic parameters significant difference. Valve disease Vd Vd than the congenital heart disease group (P lt; 0.05), t1/2β. Congenital heart disease group than the congenital heart disease group the long t1/2β (P lt; 0.01), Vc Vc than valvular disease group (P lt ; 0.05), CL CL than valvular disease group (P lt; 0.05) (see table4). Conclusion: 1, two groups of sufentanil pharmacokinetics are in line with the three-compartment model, you can use the three-exponential function. 2, the two groups of the pharmacokinetic parameters significant difference exists. Valvular disease group half-life t1/2β of congenital heart disease group t1/2β after surgery for valve disease should be given adequate respiratory support. 3, Transit sufentanil plasma concentration dropped dramatically, mainly due to hemodilution. 4, there was a significant difference in pharmacokinetic parameters of domestic sufentanil with foreign pharmacokinetic parameters. 5, the data analysis techniques can affect the pharmacokinetic parameters and correlation.
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