OBJECTIVE:To establish and validate the method for the determination of carbamazepine (CBZ) in human plas-ma,and to apply the method for external quality assessment. METHODS:After precipitated with acetonitrile,the plasma sample was determined by LC-MS/MS. Using loratadine as internal standard,the determination was performed on Kromasil C18 column with mobile phase consisted of water (containing 0.1% formic acid)-acetonitrile (gradient elution) at flow rate of 0.6 ml/min and column temperature of 40 ℃. The ion transitions under MRM mode by ESI+ ionization were performed at m/z 237.1→194.0 and m/z 383.1→267.0 for CBZ and internal standard,respectively. RESULTS:The linear range of CBZ were 5-1 000 ng/ml (r>0.998). The limit of quantitation was 5 ng/ml. RSDs of inter-day and intra-day were 1.00%-6.42%;relative deviation were -6.93%-0.32%. The external quality assessment of 5 samples were 679.0,475.0,104.0,29.2 and 26.2 ng/ml,respectively. The pass rate of assess-ment result was 100%. CONCLUSIONS:The method is sensitive,accurate and specific. The method is applicable for the plasma concentration determination and external quality assessment of CBZ.

Objective:To evaluate the uncertainty in the determination of lamotrigine(LTG)in human plasma by LC-MS/ MS. Methods:The uncertainty sources in the determination of LTG were analyzed and the uncertainty was evaluated and combined. Re-sults:The expanded uncertainty of LTG at low(0. 050 4 μg· ml - 1 )and high(1. 27 μg· ml - 1 )concentrations was 0. 005 18 μg· ml - 1 and 0. 066 4 μg· ml - 1 ,respectively(P = 95% ,k = 2). Conclusion:The uncertainty in the determination of LTG in human plasma by LC-MS/ MS is mainly caused by the protein precipitation recovery,matrix effect and sample preparation at low concentration, and by the matrix effect,sample preparation and repeatability at high concentration.

To explore the stability of Shenkang injection respectively in five different solutions to choose the best com-patibility program and improve the rational drug use. Methods:The pH value, insoluble particles and the content of protocatechuic al-dehyde in Shenkang injection were determined after mixed with five solutions. Results:In the 6-hour mixing, the change order of proto-catechuic aldehyde content was 0. 9% sodium chloride injection> 5% fructose injection> 10% invert sugar injection > 5% dextrose injection> 10% glucose injection, especially in 0. 9% sodium chloride injection, the content was decreased by 20%. The number of insoluble particles was increased after the 2-hour mixing except in 10% invert sugar injection solution, and the increase in the four so-lutions was beyond the requirement in the 2010 edition of Chinese Pharmacopoeia, and the number of insoluble particles in 0. 9% sodi-um chloride injection was the highest with the fastest change. During the experimental process, the pH value was stable. Conclusion:The five solutions show influence on stability of Shenkang injection in varying degrees. Shenkang injection in 0. 9% sodium chloride in-jection is the least stable, which should be used with caution in clinics, while invert sugar injection and glucose injection can be the best choice for Shenkang injection and the mixed solution should be used up in 2h.

Objective:To evaluate the uncertainty in carbamazepine ( CBZ) determination in human plasma by HPLC-MS/MS. Methods:The whole process of CBZ determination was analyzed and the uncertainty sources were established, and then the uncertainty was evaluated and combined, and the expanded uncertainty was also calculated. Results: The expanded uncertainty of CBZ with low (7.46 ng·ml-1) and high (745 ng·ml-1) levels was 0.410 ng·ml-1 and 33.400 ng·ml-1, respectively (P=95%, k=2). Conclusion:The uncertainty in CBZ determination in human plasma by HPLC-MS/MS is mainly caused by recovery, sample prepara-tion and matrix effect for low concentration, and by sample preparation and repeatability for high concentration.

OBJECTIVE:To establish the method for the determination of tigecycline (TGC) in human plasma. METHODS:After precipitated by acetonitrile,the plasma sample was determined by LC-MS/MS. Using d9-TGC as internal standard,Kromasil C18 column was used with mobile phase consisted of water (containing 0.05% TFA)-acetonitrile (gradient elution) at flow rate of 0.6 ml/min,column temperature of 40 ℃. The ion transitions were performed under ESI positive MRM model at m/z 586.3→513.2 and m/z 595.3→514.3 for TGC and internal standard,respectively. RESULTS:The linear range of TGC was 25-2 000 ng/ml (r=0.999 8),and lowest quantification limit was 25 ng/ml;intra-day and inter-day RSD was 3.15%-7.23%,and relative error was-4.53%-10.48%. Plasma sample kept stable after 3 times of freezing and thawing cycle,at room temperature for 24 h,in automat-ic sample injector for 24 h and freezing for 42 d (RSD<15%). Plasma concentration of TGC was 0-438.0 ng/ml in one patient with pan-drug resistant bacteria infection(0-12 h after administration). CONCLUSIONS:The developed method is accurate,sensi-tive and specific,and can be used for plasma concentration determination of TGC and pharmacokinetic study.

Objective:To establish an HPLC-MS/MS method for the determination of lamotrigine ( LTG) in human plasma to be applied in the clinical therapeutic drug monitoring. Methods:LTG was analyzed on a Kromasil C8 (50 mm × 2. 1 mm,5μm) column. Methanol and water (both containing 0. 1% formic acid) was used as the mobile phase with gradient elution. The flow rate was 0. 6 ml ·min-1 at the column temperature of 40℃. The ion transitions under an ESI positive model were performed at m/z 256. 0>211. 0 and m/z 264. 1>154. 0 for LTG and ticlopidine (internal standard, IS), respectively. Results: The calibration curve of LTG was linear within the range of 0. 02-2 μg · ml-1 . The recoveries of LTG at three quality control levels were within the range of 91. 94%-100. 28%. LTG was stable under all tested conditions and the dilution (the dilution factor was 10) had no influence on the accuracy and precision of LTG determination. Conclusion:The HPLC-MS/MS method for the determination of LTG developed in the study is accuracy, stable and convenient, and is applicable in the clinical therapeutic drug monitoring of LTG.

Objective:To provide basis for the rational use of valproic acid(VPA) in the patients with epilepsy through the analy-sis on the therapeutic monitoring data. Methods:The VPA plasma concentration and the other related information of 233 cases were analyzed retrospectively. Results:The total daily dose of VPA increased with age (P<0.05) in children group. Compared with that in adults group (19-50 years old),the target rate of VPA concentration was significantly higher in children group(4-14 years old) (P<0.001). VPA had similar antiepileptic effect in children and adults. Oral solution was the main dosage form for children and con-ventional tablets for adults. Children had higher target rate of VPA concentration than adults (P<0.05). Compared with the group with VPA alone,VPA combined with enzyme inducers such as carbamazepine,phenobarbital and phentoin significantly decreased the target rate of VPA concentration(P<0.001). Moreover,VPA combined with phenobarbital significantly decreased the total daily dose of VPA (P<0.05). Conclusion:With great inter-individual variance,VPA plasma concentration is associated with efficacy and side effects. Monitoring of VPA plasma concentration is useful to the individualized treatment of VPA.

Objective:To evaluate the interaction between remimazolam and propofol for sedation during hysteroscopy.Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 20-45 yr, with body mass index of 18-28 kg/m 2, scheduled for elective hysteroscopy, were included. The test was conducted in two steps. Up-and-down sequential allocation was used to determine the median effective dose (ED 50) of remimazolam (group A) and propofol (group B). The ED 50 obtained in A and B groups were then used as the standard to determine the combination regimen in group C (0.25×ED 50 of remimazolam+ 0.75×ED 50 of propofol as the initial dose), in group D (0.5×ED 50 of remimazolam+ 0.5×ED 50 of propofol as the initial dose), and in group E (0.75×ED 50 of remimazolam+ 0.25×ED 50 of propofol as the initial dose). Up-and-down sequential allocation was used to determine the ED 50 of propofol when propofol and remimazolam were combined in C, D and E groups. The interaction between the sedative effects of two drugs was analyzed using the isobolographic analysis method, and the interaction coefficient and synergistic dose ratio of two drugs were calculated. Results:The ED 50 of remimazolam was 0.180 mg/kg in group A, and the ED 50 of propofol was 1.167 mg/kg in group B. The results of isobolographic analysis showed that remimazolam and propofol had a synergistic effect. When remimazolam 0.045, 0.090 and 0.135 mg/kg were combined with propofol 0.546, 0.288 and 0.160 mg/kg, the interaction coefficients were 1.393, 1.339 and 1.127 respectively. The synergistic dosage ratio of remimazolam and propofol was 1.0∶(3.2 to 12.0). Conclusions:Remimazolam and propofol have a synergistic effect on sedation when used for hysteroscopy, and the dose ratio is 1.0∶(3.2-12.0).