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.