A two_dimensional HPLC method was developed for the determination of methotrexat ( MTX ) in human plasma. The samples were treated with trichloroacetate for sedimentation and high speed centrifugation, and the obtained supernatant was taken for analysis. The analytes in sample were separated on the first dimension column (ASTON C8 100 mm × 4. 6 mm, 5μm), and trapped on the middle column (ASTON SCX 20 mm × 4. 6 mm, 5 μm) using valve_switching technique for purification and storage. Finally, the trapped analytes were transferred to the second_dimension column (SAC C8 100 mm × 4. 6 mm, 5μm) for the second separation. The mobile phase used for the first dimension was 10 mmol/L ammonium acetate_acetonitrile(9∶1, V/V, pH=3. 8) with a flow rate of 1 mL/min and the mobile phase used for middle column was 10 mmol/L phosphoric acid ( pH=3 . 0 ) . The mobile phase used in second_dimension was a mixed solution of 50 mmol/L ammonium acetate and acetonitrile (87∶10, V/V, pH=5. 2). UV detection was carried out at 306 nm and completed in 4 min. The calibration curve showed a linearity range from 0. 0879 to 5. 154 μmol/L (r=0. 99998). The LOQ was 0. 005 μmol/L. The intra_and inter_day precisions were lower than 1. 5% and 1. 8%, respectively. The relative recovery and the absolute recovery were 99. 1% - 101. 2% and 85. 67%-86. 35%, respectively. The assay is simple, accurate, reproducible, and suitable for the therapeutic drug monitoring of MTX in the hospital and the study on the pharmacokinetics of MTX.

OBJECTIVE:To establish a method for determination of carbazochrome sodium sulfonate for injection.METH_ ODS:C 18 was used as chromatographic column;the mobile phase consisted of0.12%ammonium dihydrogen phosphate buffer solution-absolute alcohol(925∶75)with detection wavelength at363nm and flow rate at0.8ml/min.The sample size was10?l and the column temperature was25℃.RESULTS:Linear relation was achieved when the concentration of carbzochrome sodium sulfonate was within the range of0.08865mg/ml～0.4432mg/ml(r=0.9999,n=5).The mean recovery rate was99.89%(RSD=1.53%,n=9).CONCLUSION:This method is simple,rapid,accurate,precise,and which can be used as the quality control of carbzochrome sodium sulfonate for injection.

Objective: To investigate the effect of UGT2B7 A268G and UGT2B7 G211T genetic polymorphism on serum drug concentration of valproic acid (VPA).
Methods:Genetic polymorphisms of UGT2B7 A268G and UGT2B7 G211T were tested in 248 epileptic patients by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Data including basic information, epilepsy type, times and doses of drug, treatment response and liver and kidney functions were collected. Statistical analysis was performed by SPSS 13.0 through multivariate linear regression, one-way ANOVA,χ2 test, and paired T-test.
Results:Based on multivariate linear regression, there was no significant difference between gender, age, or body mass index and VPA, but concentration-to-dose ratios (CDRs) were positively correlated with VPA. hTe genetic polymorphisms of UGT2B7 A268G and UGT2B7 G211T were consistent with Hardy-Weinberg equilibrium. UGT2B7-268A>G allele frequency distribution A was 30.05%, and G was 69.95%. Variance analysis showed that serum drug concentration was significantly different in the genotype of AA, AG, or GG (F=5.477, P=0.005). Further analysis of paired T test showed that AA type was significantly different from GG type (P=0.048), and that serum concentration of AA type was much higher than that of GG type, while no signiifcant difference between AA type and AG type, GG type and AG type. UGT2B7 G211T allele frequency distribution G was 77.24%, and T was 22.58%. hTere was no signiifcant difference in standardized serum concentration among genotypes of GG, GT, and TT.
Conclusion:hTis study reveals UGT2B7 A268G genetic polymorphism distribution in Chinese epilepsy population. UGT2B7 A268G plays an important role in VPA’s metabolism, and has certain effect on VPA’s serum concentration. Epilepsy patient with this genotype should be adjusted the dose of VPA to make a therapeutic effect.

Objective: To analyze the serum concentration results of sodium valproate (VPA) and carbamazepine (CBZ) and explore the relationship between the serum concentration and age, clinical efficacy and adverse reactions to provide reference for the rational clinical use.Methods: Retrospective analysis was used to collect the clinical data of the patients from March 2015 to March 2016, including gender, age, clinical diagnosis, medication, usage and dosage, the last medication time, sampling time, blood concentration and the other related data, and the data were compared and analyzed.Results: Totally 2608 samples were collected, including 2 205 ones for VPA and 403 ones for CBZ.Totally 1 123 cases (50.93%) of VPA and 292 cases (72.46%) of CBZ were within the range of therapeutic windows.In the 2 205 cases of VPA, 1 814 cases (82.27%) were with single drug treatment, and the serum concentration lower than the lower limit of therapeutic window accounted for 790 cases (43.55%) with the effective rate of 43.55% for epilepsy.The serum concentration within the range of therapeutic window accounted for 921 cases (50.77%) with the effective rate of 88.27% for epilepsy, and that higher than the higher limit of therapeutic window accounted for 103 cases (5.68%) with the effective rate of 81.55%.As for CBZ, the number was 58 cases (22.39%) with the effective rate of 48.28%, 195 cases (72.29%) with the effective rate of 79.49% and 6 cases (2.32%) with the effective rate of 83.34%, respectively.Totally 391 cases (87.21%) of VPA combined with the other antiepileptic drugs, such as levetiracetam and lamotrigine.The effect of age on the serum concentration of VPA and CBZ was significant (P<0.05).Conclusion: There are great individual differences in serum concentration of VPA and CBZ among patients.The therapeutic effect and adverse reactions of VPA and CBZ are closely related to the serum concentration.Monitoring the serum concentrations may provide evidence for the rational administration and plays an important role in the treatment of epilepsy.

OBJECTIVE:To change traditional working mode of drug storehouse by applying intelligent system,improve drug storage management,improve work efficiency and quality of drug storehouse,and to provide reference for hospital drug storehouse information management. METHODS:The changes of drug storehouse working mode and management in our hospital were compared before and after the application of intelligent drug storehouse management system. The time taken to complete individual work and the times of error occurrence 12 weeks before and after the application of the system were adopted as indexes to evaluate the effects of the system. RESULTS:Through the combination of Internet+Internet of things bar code,radio frequency identification,electronic tags,etc.,intelligent drug storehouse management system,which included temperature and humidity management,drug storehouse management,supply chain management three modules,was established in our hospital. Its application improved the drug storehouse working mode and process,strengthened the drug storehouse management in respect of staff,supplier,cold chain drugs and special drugs. Before application,average weekly time-consuming of drug shelfing,bill warehousing,outgoing and deliverying and inventory were(11.92 ± 0.701)h,(13.96 ± 0.752)h,(14.96 ± 0.542)h,(4.58 ± 0.376)h;the times of errors within 12 weeks were 10,8,9,2,respectively. After application of the system,average weekly time-consuming were(9.83±0.718)h,(11.29±0.753)h,(9.91±0.557)h,(3.00±0.316)h,respectively(vs. before application, all P<0.05). The times of errors within 12 weeks were 1,1,2,0. CONCLUSIONS:The application of intelligent drug storehouse management system optimizes workflow of drug storehouse in our hospital,strengthens the management of drug storehouse,and improves working efficiency and quality of the drug storehouse.

OBJECTIVE: To exlpore the eff ect of depsides salts from Salvia miltiorrhiza on human hepatoma cell line SMMC-7721 xenograft tumors and the possible mechanisms. METHODS: A total of 36 nude mice were divided into 6 groups: A model group, a negative control group, a positive control group, and 3 treatment groups at low, middle or high dose (n=6). The tumor model of nude mice was given depsides salts at a dose of 10, 20 or 50 mg/kg every 3 day for 16 days. Then samples of subcutaneous tumors in nude mice were collected. The morphological changes of tumor samples were observed by HE staining and the expression of vascular endothelial growth factor (VEGF) and the tumor antigen Ki67 was detected by immunohistochemical method. RESULTS: The tumor growth was inhibited by all doses of depsides salts. The morphology of tumors was shrinkage, broken and irregularly arranged compared with the tumors in the model group and the negative control group. Morphological changes were more obvious in tumors with treatment at high dose. Expression of VEGF and Ki67 in treatment groups and the positive control group were lower than that in the model group and the negative control group, with a significant difference (P<0.05). CONCLUSION Depsides salts from Salvia miltiorrhiza can inhibit the growth of human hepatoma cell line SMMC-7721 tumor in nude mice, which is related to the inhibition of Ki67 and VEGF.
Animals ; Carcinoma, Hepatocellular ; pathology ; Cell Line, Tumor ; drug effects ; Depsides ; pharmacology ; Humans ; Ki-67 Antigen ; metabolism ; Liver Neoplasms ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Salts ; Salvia miltiorrhiza ; chemistry ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays

Valproic acid is a first-line broad-spectrum antiepileptic drug, however, the pharmacokinetics of valproic acid are affected by many factors, such as heredity, drug combination and so on. So, how to realize the individualized dosing regimen of valproic acid has received much attention. Population pharmacokinetics combines classical pharmacokinetic principles and population statistical models to quantitatively evaluate the influence factor of drug concentration in the patient population. Thus, it can optimize characterization of the differences among individuals. This article reviews the researches about valproic acid in recent years, and summarizes the effect of the factors on the metabolism of valproic acid, such as drug combination and gene polymorphism. Additionally, focus on the latest research progress of individual administration of valproic acid under the guidance of population pharmacokinetics.

OBJECTIVE: To investigate whether single nucleotide polymorphisms (SNPs) of rs2298771 and rs3812718 of the sodium channel α-subunit type 1 (SCN1A) gene affect the efficacy of carbamazepine (CBZ) treatment for seizures in Chinese Han epileptic patients. METHODS: SNP rs2298771 and rs3812718 of the SCN1A gene from 628 patients were genotyped. CBZ monotherapy was administered to the subjects with new-onset partial seizures. The efficacy was defined as the decrease in the number of seizures. Four semi-quantitative levels were used to assess the efficacy: seizure-free (SF), >75% seizure decrease (SD), 50%-75% SD, and <50% SD in the number of seizures compared with patients' initial conditions. RESULTS: After the 12 month treatment with CBZ monotherapy, the rate of SF patients with G allele of the SNP rs2298771 was significantly lower than that in patients with the AA genotype (P=0.003). The heterozygote and homozygote of the G allele at SNP rs2298771 predicted the low SF rate (OR=2.101, 95% CI 1.289-3.425). Marginal significance was observed between the dichotomous efficacy of SF and non-SF in 3 partial seizure types (P=0.028). CONCLUSION rs2298771 is significantly associated with the efficacy of CBZ monotherapy in Chinese Han epileptic patients.
Alleles ; Asian Continental Ancestry Group ; Carbamazepine ; therapeutic use ; Epilepsy ; Genotype ; Humans ; NAV1.1 Voltage-Gated Sodium Channel ; genetics ; Polymorphism, Single Nucleotide ; Seizures ; drug therapy ; genetics