目的 研究高效液相色谱-质谱联用法（HPLC-MS/MS）测定血浆中二亚油酰磷脂酰胆碱（DLPC）浓度测定的方法。 方法 2010年11月－2011年1月，7例受试者，3例服用多烯磷脂酰胆碱软胶囊（试验制剂），3例服用多烯磷脂酰胆碱胶囊（参比制剂），1例未服药；采集服药者血浆，对各种检测方法、样品预处理条件进行考核；用建立的方法对6例服药者和1例未服药者血浆DLPC浓度进行测定。 结果 最终建立的方法为：采用API 3000型HPLC-MS/MS液质联用系统，多反应离子检测模式，正离子扫描，大气压化学电离源，色谱柱为Ultimate CN分析柱（50.0 mm × 4.6 mm，5 ?m），流动相为甲醇︰水︰甲酸（80︰20︰0.05，V/V/V），流速为0.5 mL/min，格列齐特作为内标。受试者口服多烯磷脂酰胆碱软胶囊试验制剂与参比制剂后，DLPC血浆浓度水平均未见明显的变化规律。未服药者血浆DLPC浓度也有较高浓度水平。 结论 所建立的HPLC-MS/MS法，未能用于多烯磷脂酰胆碱软胶囊生物等效性评价。
ObjectiveTo establish an accurate and sensitive high performance liquid chromatography-mass spectrometric (HPLC/MS/MS) method for determination of vorinostat (SHA) and M2 metabolites in human serum, which was applicable for pharmacokinetic study of SHA. MethodsThe essay was conducted with an API 3000 HPLC-MS/MS system consisted of a Gemini C18 column (50 mm×3 mm, 3 μm), and the mobile phase consisted of methanol-acetonitrile-water-1 mol/L NH3-formic acid (25:15:60:0.1:0.05) at a flow rate of 0.23 mL/min. Acidulated serum samples were extracted by 3.5 mL diethyl ether which contains 3% isopropyl alcohol and was operated under the multiple reaction monitoring mode using the electrospray ionization technique. d5-SHA was used as the internal standard. ResultsThe retention time of SHA, M2 metabolite and internal standard were 4.1, 3.1 and 4.0 minutes, respectively. The linear range of SHA and M2 metabolite were in the range of 1-1 000 and 2-2 000 ng/mL, and the limit of quantity were 1.0 and 2.0 ng/mL; the method recovery were 93.0%-99.3% and 88.11%-104.12%, respectively. Matrixes effect of SHA and M2 metabolite were blow 9.0%. ConclusionThis method for the quantitative determination of SHA and M2 in human serum was proved to be simple, rapid, sensitive and accurate; it can be applied in the determination of SHA and M2 metabolite.
ObjectiveTo systematically review the factors influencing plasma concentration of lamotrigine (LTG) in the treatment of epilepsy in children.Methods Databases including PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data, VIP and CBM were electronically searched to collect clinical studies on the factors influencing plasma concentration of LTG in the treatment of epilepsy in children from database inception to December 2020. Two researchers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. A systematic review was then performed to analyze the factors influencing plasma concentration of LTG in the treatment of epilepsy in children. ResultsA total of 21 studies were included. The results of systematic review suggested that dosage and some combination drugs (valproic acid, carbamazepine, phenytoin sodium, topiramate, ethosuximide, rufinamide, fluoxetine, clonazepam, clobazam and ethinylestradiol) were potential factors influencing LTG concentration. Four gene polymorphisms (UGT1A4 142T>G, UGT1A4 219C>T, UGT1A4 163G>A, and OCT1 M408V A>G), age, weight, sex, and combination drugs (phenobarbital and levetiracetam) might affect the plasma concentration of LTG in children. The effects of oxcarbazepine, 16 gene polymorphisms (UGT1A4 *3 T>G, UGT2B7 211G>T, UGT2B7 372A>G, UGT2B7 735A>G, UGT2B7 801T>A, UGT2B7 802C>T, UGT2B7 161C>T, SCN1A IVS591G>A, SCN2A c.56G>A, SCN2A c.59G>A, MDR1 1236 C>T, MDR1 2677 G>T/A, MDR1 3435 C>T, SLC22A1 1022C>T, ABCB1 3435 C>T and ABCB1 1236C>T), ketogenic diet, and ethnicity (Uygur/Han) on the plasma concentration of LTG in children were not found. Conclusion The plasma concentration of LTG in the treatment of epilepsy in children is affected by many factors, and more high-quality prospective studies should be carried out to further clarify the factors influencing the plasma concentration of LTG in children.
Objective To study the correlation of changes in liver function during long-term treatment with sodium valproate (VPA) in children with epilepsy in Putian, and to explore individualized administration to improve the compliance of children with medication. Methods The blood concentration of VPA and related biochemical test data of 350 children with epilepsy from June 1, 2018 to March 1, 2021 were collected in our hospital. According to the results of VPA blood concentration, they were classified as low Blood concentration group (<50 μg/mL), therapeutic blood concentration group (50 ~ 100 μg/mL) and high blood concentration group (>100 μg/mL). Results There was no significant difference in liver function indexes between the VPA treatment group and the control group (P>0.05). There were significant differences in liver function ALT, AST, AST/ALT, TBIL and DBIL among the groups of VPA blood concentration range (P<0.05). The abnormal incidence of liver function indexes of high blood drug concentration was lower in the concentration group and higher in the treatment concentration group, and there were differences (P<0.05). Conclusion Abnormal liver function in the high blood drug concentration treatment groupis quite common, and the dose of the drug should be adjusted in time to avoid liver damage caused by the VPA.