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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.
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Aromatic antiepileptic drugs such as carbamazepine are the first-line treatment for epilepsy. The adverse reactions have greatly limited their clinical application. The occurrence rate of severe skin adverse reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) is low,but they are often fatal.Human leukocyte antigen (HLA) gene polymorphisms are reported to be related with skin adverse reactions caused by aromatic antiepileptic drugs,but the exact mechanism is unclear.This article will perform a review about the correlation between skin adverse reactions caused by aromatic antiepileptic drugs and HLA gene polymorphisms published in recent years,in order to provide theoretical basis for further study of HLA susceptibility genes in Chinese Han population,and provide a reference for achieving individualized treatment of epilepsy.
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Objective To evaluate the uncertainty for the determination of salicylic acid in human plasma by ultra performance liquid chromatography(UPLC).Methods All sources of uncertainty in the whole process of salicylic acid determination were analyzed,then the combined and expanded uncertainty were evaluated.Results The expanded uncertainty at concentrations of the lowest limit of quantitation(0.23 μg·mL-1) and a high level(39.43 μg·mL-1) of salicylic acid(P=95%,k=2) was 0.014 and 7.34 μg·mL-1,respectively.Conclusion The uncertainty of salicylic acid determination in human plasma by UPLC was mainly caused by recovery,repeatability and sample preparation at the lowest limit of quantitation and high qulity control concentration.
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Objective To evaluate the uncertainty of the pseudo-ginsenoside GQ (PGQ) concentration in human plasma by HPLC-MS/MS.Methods The whole process of PGQ determination by HPLC-MS/MS in human plasma was evaluated and the uncertainty caused by repeatability,weighing,standard solution preparation,biological sample preparation,extraction recovery process,recovery,instrument precision and calibration curve fitting were evaluated,respectively.The combined and expanded uncertainty values were both calculated.Results The expanded uncertainty values for low (15.16 ng·mL-1),medium (2 516.67 ng·mL-1) and high (3 902.00 ng·mL-1) levels of PGQ were 1.39,177.74 and 262.69 ng·mL-1,respectively (P =95 ％,k =2).Conclusion The uncertainty of the PGQ determination in human plasma by HPLC-MS/MS is mainly caused by recovery,repeatabihty and sample preparation at low concentration,by sample preparation and recovery at medium and high concentration.
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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.
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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.
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Objective:To evaluate the uncertainty in 6-methylthiopurine (6-MMP) determination by LC-MS/MS. Methods:The uncertainty sources during the whole process of 6-MMP determination were established and evaluated. The combined and expanded un-certainties were also calculated. Results:The expanded uncertainty at low (2 995 pmol) and high (140 900 pmol) concentration of 6-MMP was 275. 6 pmol and 11 396 pmol, respectively (P=95%, k=2). Conclusion: The uncertainty in 6-MMP determination by LC-MS/MS is mainly caused by recovery, matrix effect and sample preparation at low concentration, and by recovery and sample prep-aration at high concentration.
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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.
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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.
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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.
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OBJECTIVE:To evaluate the uncertainty of the determination of clopidogrel active metabolite derivative(CAMD) in human plasma by LC-MS/MS. METHODS:The course of CAMD determination in human plasma by LC-MS/MS were analyzed to evaluate the uncertainty caused by evaluate repeatability,weighing,standard solution preparation,biological sample prepara-tion,recovery,instrument precision and calibration curve fitting in CAMD assay;the uncertainty were calculated and expanded. RESULTS:The expanded uncertainty for low(0.107 ng/ml),medium(4.467 ng/ml)and high(155.667 ng/ml)levels of CAMD were 0.010 2 ng/ml,0.188 ng/ml and 6.413 ng/ml,respectively(k=2,P=95%). CONCLUSIONS:The uncertainty of the CAMD determination in human plasma by LC-MS/MS at low concentration is mainly caused by calibration curve fitting;at medium and high concentrations is mainly caused by biological sample preparation,extraction procedure,standard solution preparation and in-strument precision.