Determination of Valsartan in Human Plasma and Urine by LC-MS/MS and Its Pharmacokinetic Study / 中国药房

OBJECTIVE:To develop a method for the determination of valsartan concentration in human plasma and urine. METHODS:Plasma sample were acidified and extracted with diethyl ether for analysis,and urine sample was diluted directly for analysis. The samples were all determined by LC-MS/MS,and the separation was performed on a Aglient ZORBAX SB-C18 column with mobile phase consisted of acetonitrile and 0.1% formic acid (gradient elution) at flow rate of 0.2 ml/min. Ion transition was determined ESI ion source under multiple ion reaction monitoring with quantitative pair m/z 436.4→253.2 and qualitative ion pair m/z 436.4→291.3 for valsartan,and quantitative pair m/z 423.4→207.1 and m/z 423.4→180.2 for internal standard losartan. RE-SULTS:The linear range of valsartan were 4-5 000 ng/ml in plasma and 20-50 000 ng/ml in urine;the limit of quantification were 4 ng/ml and 20 ng/ml;plasma extraction recovery of valsartan were 61.21%-70.30%. The variation coefficient of internal standard normalized matrix effect were 3.20% and 11.21%. The within-day and between-day RSDs were no more than 8.34%. CONCLU-SIONS:The method is proved to be rapid and sensitive,and suitable for the determination of valsartan in human plasma and urine and pharmacokinetics study.

Pharmacokinetics of cephapirin sodium in healthy volunteers / 中国生化药物杂志

Objective To investigate the pharmacokinetics of cephapirin sodium in healthy volunteers.Methods Twelve healthy volunteers were enrolled and ad ministered with single doses of 0.5,1.0,4.0 g or multiple doses of 1.0 g cephapirin sodium injection by intravenous drip infusion.The concentrations of cephapirin in human plasma and urine were determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated with WinNonLin 6.3 software. Results The main pharmacokinetic parameters of cephapirin after single dose of 0.5,1.0,4. 0 g and 1.0 g multiple dose cephapirin sodium injection were as follows:Cmaxwere (34.86 ±6.93),(74.77 ±24.23),(319.0 ±44.5),(89.26 ±28.04)μg/mL,AUC0-twere (12.86 ±3.46),(28.31 ±7.46),(163.21 ±34.57),(27.30 ±7.22)μg/(mL·h),t1/2were (0.55 ±0.21),(0.72 ±0.22),(0.71 ±0.27), (0.72 ±0.25),accumulative urine excretion rate of 8 h(1 g)was (44.9 ±12.66)%.Conclusion The process of cephapirin in the dosage range of 0.5 ~4.0 g show linear dynamic feature.There is no accumulation after multiple dosing.Cephapirin sodium was much eli minated from urine in parent drug.

Synergistic effect of donor livers pre-perfused by recipient blood serum and cobra venom factor treatment to inhibit hyperacute rejection happened in liver xenotransplantation / 中华肝胆外科杂志

ObjectiveTo investigate synergistic effect of donor livers blocked by recipient blood serum (RS) and cobra venom factor (CVF) treatment to inhibit hyperacute rejection (HAR) happened in liver xenotransplantation.MethodsThe SD rat blood serum was prepared for pre-perfusing the donor livers before experiment.24 pairs of guinea-pig (GP) and Sprague-Dawley (S.D.) rats were choiced respectively and pair-matched between GP donor and rat recipient randomly.Before transplantation,donor livers of GPs were pre-perfused by 0.5％ SD rat serum.Paired animals were divided into 4 groups randomly such as donor liver perfused by RS,recipient treated by CVF,RS+ CVF performed and Ringer solution as a control.The orthotopic liver xenotransplantations was performed with two-cuff technique.The survival time and liver function of recipients,morphological and pathological changes of rat livers were observed.ResultsThere was no piebaldism change on the recipient liver from experimental group.The survival time of recipients from RS+CVF group [(161.5±30.9) min]was longer than that of control[(45.2 ± 13.9) min] and CVF[(125.2 ± 25.5) min] or RS groups [(88.1±19.7) min] (P＜0.05).The ALT in serum of recipients from RS+CVF [(63.2±13.9)U/L]was lower than that from congtrol group [(126.1±23.3)U/L](P＜0.01) and CVF group [(79.9±18.1)U/L](P＜0.05) or RS group [(106.1±19.3)U/L](P＜0.01) The histological damages including thrombosis,interstitial bleeding and edema of recipient liver from RS+CVF group were alleviated markebly than that of other groups (P＜0.05).ConclusionThere was a synergistic effect to inhibit HAR happened in liver xenotransplantation by blocking the donor liver with recipient blood serum and CVF treatment significantly.

Recipient blood serum in the prevention of hyperacute rejection of liver xenotransplantation / 中华普通外科杂志

ObjectiveTo investigate a new way to prevent hyperacute rejection (HAR) during liver xenotransplantation through blocking the xenograft with recipient blood serum before transplantation.MethodsTwenty guinea-pig (GP) and Sprague-Dawley (SD) rats were pair-matched as donor and recipient randomly.Before transplantation,blood serum collected from other SD rats was inactivated at 45 ℃ in water bath for 30 minutes.Guinea-pig donor livers from experimental group ( n =10 ) were pre-perfused by 0.1％ solution of this blood serum,and donor livers from control group (n =10) were treated by Ringer solution.Then orthotopic liver xenotransplantations were performed by the modified two-cuff technique immediately.Liver morphology changes and survival rate and time of recipients were observed,and histopathological lesions were detected by HE staining,and liver ALT level was evaluated.ResultsThe operation time and anhepatic phases between two groups were not different significantly ( P ＞ 0.05 ).The survival rate of recipients from experimental group was higher,and its survival time was longer than that of control group significantly (P ＜ 0.01 ).The liver histological changes such as thrombosis and interstitial bleeding in experimental group was less severe than that in control group (P ＜0.01 ).The level of ALT in blood serum of rats from experimental group were lower than that from control group significantly ( P ＜ 0.05).ConclusionsThe results suggested that blocking the donor graft with recipient blood serum inhibits HAR during liver xenotransplantation.

Analysis on clinical features, viral load and viral shedding period of patients with mild or severe H1N1 influenza A virus infection / 中华传染病杂志

Objective To analyze clinical and laboratory features, viral load and viral shedding period of patients with mild or severe H1N1 influenza A infection. Methods Seventy mild cases and 16 severe cases with concurrent pneumonia were included from Shcnzhen area for analysis.Nasopharyngeal-swab specimens of patients were collected and viral load was detected by real-time quantitative polymerase chain reaction (PCR) assay during their hospitalization. The viral load and viral shedding period were compared between patients over 14 years old and less than 14 years old, and between 70 mild cases without pneumonia and 16 severe cases with pneumonia. The statistic analysis was performed using t test and chi square test. Results The most common symptoms and signs of the patients were fever, cough and enlargement of tonsils. However, the severe cases suffered more frequently from cough, dyspnea and high fever compared with the mild cases (x2 = 10. 9 and 14.3, respectively, t=3.65; both P＜0.01 ). The levels of white blood cell (WBC) count and alanine arninotransferase (ALT) of severe patients were both significantly higher than those of mild patients(t= 3.2, 2.4,respectively; both P＜0.05). The chest radiology of the severe cases showed interstitial pneumonia,mostly with ground glass image. The viral load of patients under 14 years was significantly higher than those over 14 years [(4.86± 1.23) lg vs (4. 17±0.89) lg; t=2.3, P＜0.05], and the viral shedding period of patients under 14 years was significantly longer than those over 14 years [(5.33±0. 49) d vs(3. 63±0.28) d; t=3.4, P＜0.01]. The severe patients also displayed significantly higher viral load and prolonged viral shedding period than the mild patients [(6. 36±1. 44) lg vs (4. 35±0.99) lg, t=6.1,P＜0.01; (5.75±1.77) d vs (4. 24±1. 96) d, t=3.2, P＜0.01]. Conclusion Age anddisease severity of patients with H1N1 influenza A infection are significantly associated with viral load and viral shedding period.