Simultaneous determination of verapamil and its metabolite norverapamil in human plasma by liquid chromatography-tandem mass spectrometry / 药学学报

A sensitive and simple high-performance liquid chromatographic tandem mass spectrometric (LC-MS/MS) method for the determination of verapamil and norverapamil in human plasma was established and utilized in a pharmacokinetic study in healthy patients. Protein was precipitated by methanol in plasma samples, and the analytes and internal standard were separated on an Agilent Zorbax Eclipse C18 column (50 mm×4.6 mm, 5 μm) with a gradient procedure using methanol-acetonitrile (50∶50) as the organic phase and 0.1% formic acid - 5% acetonitrile - 10 mmol·L-1 ammonium formate solution as the mobile phase at flow rate of 0.5 mL·min-1. Electrospray ionization (ESI) and multiple reaction monitoring (MRM) detection modes were used for quantitative detection of verapamil, norverapamil and verapamil-d6 (IS). In the mode of multiple reaction monitoring of positive-ions, the monitoring ion pairs of verapamil, norverapamil and the verapamil-d6 were m/z 445.0→165.2, m/z 441.0→165.2 and m/z 461.1→165.2, respectively. The quantitative lower limit (LLOQ) for the determination of verapamil and norverapamil concentrations in human plasma can reach 0.1 ng·mL-1 in this assay. The calibration curve concentration ranged from 0.1 to 50 ng·mL-1 with high linearity (r2 > 0.997). The matrix effect of verapamil and norverapamil was 99.2%-100% and 101%-102%, respectively. The recovery of verapamil and norverapamil was 86.8%-95.9% and 87.4%-94.8%, respectively. This method has good specificity and high sensitivity. The determination of the verapamil and norverapamil was not subject to the matrix effect and stable extraction recovery was achieved in this assay. This method could be used to determine the concentration of verapamil and norverapamil in human plasma and suitable for human pharmacokinetic studies after approved by ethics committee.

Quantification of norfloxacin in human plasma by LC-MS/MS and validation of the analytical method / 药学学报

A LC-MS/MS method for quantification of norfloxacin in human plasma had been developed. This method was applied to the pharmacokinetics study of norfloxacin in the human. The plasma sample was precipitated by methanol and ciprofloxacin was used as the internal standard (IS). Chromatographic separation was performed on a Symmetry® C18 column(100 mm×4.6 mm, 5 μm). Mobile phase contains 0.3% formic acid and 5% methanol in deionized water at a flow rate of 0.45 mL·min-1. Norfloxacin and ciprofloxacin (IS) were ionized with an ESI source and operated in positive ion mode. The detected ions were m/z 320.3→302.1 (norfloxacin), m/z 332.3→314.1 (ciprofloxacin). This LC-MS/MS method yielded a linearity over the range of 10-1 000 ng·mL-1 with the lower limit of quantitation (LLOQ) of 10 ng·mL-1. The intra and inter-assay precisions (RSD%) were within the range of 2.64%-7.23% and the accuracy (RE%) was less than ±5.00%. The pharmacokinetic parameters tmax, Cmax, AUC0-t, and t1/2 were 1.28±0.364 h, 627±171 ng·mL-1, 2 938±850 h·ng·mL-1, and 6.01±1.36 h, respectively. This LC-MS /MS method was proven simple, sensitive, rapid and suitable for pharmacokinetics study of norfloxacin in the human and Approved by the Medical Ethics Committee of Liuzhou Workers' Hospital.

A rapid method for chemical fingerprint analysis of Pan Panax notoginseng powders by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry / 中国天然药物

A method coupling ultra-performance liquid chromatography (UPLC) with quadrupole time-of-flight mass spectrometer (Qtof MS) using the electrospray ionization (ESI) source was developed for the identification of the major saponins from Panax notoginseng powder (PNP). Ten different PNP samples were analyzed and evaluated for their quality by similarity evaluation and principle component analysis (PCA). Based on the accurate mass, summarized characteristic fragmentation behaviors, retention times of different types of saponins, related botanical biogenesis, and reported chromatographic behavior of saponins, fifty-one common peaks were effectively separated and identified, including 28 protopanaxadiol saponins and 18 protopanaxatriol saponins. Simultaneously, 15 significant discrepancy compounds were identified from the disqualified PNP samples. The established UPLC/Qtof MS fingerprint method was successfully applied for profiling and identifying the major saponins of PNP, providing a fast quality evaluation tool for distinguishing the authentic PNP and the adulterated products.

Present situation and development of acupuncture and moxibustion in Turkey / 中国针灸

The development and status of acupuncture-moxibustion in Turkey in the fields of education, legal establishment, treatment, etc. are introduced. There are four distinguished features of acupuncture-moxibustion development in Turkey: (1) The geographical position of the country as the link of Europe and Asia, has resulted in the special feature of acupuncture-moxibustion transmission and development. It combines both the traditional theories from the East and the modified and modern techniques from the West. (2) The combination of theories and clinical practice started when acupuncture-moxibustion was first introduced. (3) The application of acupuncture-moxibustion has gone through a process from spontaneous transmission among the people to legalization by the government, from disorderly to orderly, and from market behavior to government-lead regulation, which has powerfully promoted healthy development of the medicine. (4) Acupuncture-moxibustion education provided by registered universities has guaranteed the quality of the education itself and the competency of the professionals. It has raised the scientific and normative character of application and increased the credibility of the people, and also has ensured the sustainability of acupuncture-moxibustion development by providing qualified professionals.

Selective hydrolysis of flavonoid glycosides by Curvularia lunata / 中国天然药物

Twelve flavonoid glycosides were involved in the biotransformation of the glycosyl moieties by Curvularia lunata 3.4381, and the products were analyzed by UPLC/PDA-Q-TOF-MS(E). Curvularia lunata displayed hydrolyzing activities on the terminal Rha or Glc units of some flavonoid glycosides. Terminal Rha with a 1 → 2 linkage of isorhamnetin-3-O-neohesperidoside and typhaneoside could be hydrolyzed by Curvularia lunata, but terminal Rha with a 1 → 6 linkage of rutin, typhaneoside, and quercetin-3-O-apiosyl-(1 → 2)-[rhamnosyl-(1 → 6)]-glucoside could not be hydrolyzed. Curvularia lunata could also hydrolyze the Glc of icariin, floramanoside B, and naringin. This is the first report of the hydrolysis of glycosyl units of flavonoid glycosides by Curvularia lunata. A new way to convert naringin to naringenin was found in this research.

The impact of HBeAg positivity/negativity and HBV DNA loads on the prognosis of chronic severe hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the impact of HBeAg positivity/negativity and HBV DNA loads on the prognosis of chronic severe hepatitis B.</p><p><b>METHODS</b>206 patients with chronic severe hepatitis B hospitalized in Beijing Ditan Hospital from July 2002 to Dec. 2004 were analyzed. HBeAg positivity/negativity, HBV DNA loads and other factors relating to the prognosis of the patients were studied with univariate and multivariate analyses.</p><p><b>RESULTS</b>Chi2 univariate analysis showed that there was no significant difference in the prognosis between different HBeAg groups (chi2 = 0.440, OR = 0.777, 95% CI 0.424-1.425, P = 0.50). But there was a significant difference in the prognosis between different HBV DNA load groups: the prognosis of patients with lower HBV DNA loads was better than those with higher loads (chi2 = 9.806, OR = 3.055, 95% CI 1.554-6.007, P = 0.002), and the improving rates of the two groups were 53.1% and 27.0% respectively. Using multivariate logistic regression analysis, 9 screened factors showed great impact on the prognosis of chronic severe hepatitis B. Cirrhosis, hepatorenal syndrome, hepatic encephalopathy, PTA < 20%, TBil > 513 mmol/L, Alb < 30 g/L, CHO < 1.6 mmol/L, PLT < 5 x 10(9)/L, and higher HBV DNA loads (HBV DNA > 3 x 10(4) copies/ml in HBeAg negative patients and > 1 x 10(5) copies/ml in HBeAg positive patients) were shown to be associated with a poor prognosis. Coefficients of regression of the above factors were 1.539, 21.356, 1.398, 1.650, 2.440, 2.266, 1.738, 2.631 and 2.656 respectively. The coefficients of regression of HBV DNA loads were: B = 2.656, Wald = 7.768, P = 0.005, EXP(B) = 14.235, and 95.0% CI for EXP(B) = 2.199-92.133.</p><p><b>CONCLUSIONS</b>Our results indicate that the HBV DNA loads were one of the most important factors influencing the prognosis of the chronic severe hepatitis B patients, the importance is only next to hepatorenal syndrome and over grade II hepatic encephalopathy. HBeAg positivity/negativity has no influence on the prognosis, but HBV DNA loads are important; the lower the viral loads, the better the prognosis.</p>

Analysis of serological findings and clinical manifestations of TORCH infections in newborns / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To search for the serological findings and early clinical manifestations as evidences for prevention and treatment TORCH infections in pregnant women and newborns as early as possible.</p><p><b>METHODS</b>ELASA was performed to screen specific anti-TORCH (Toxoplasma gondii, Cytomegalovirus, Rubella virus, Herpes simplex virus) Ig-M antibodies.</p><p><b>RESULTS</b>Totally 1,554 in-patients who were treated in Neonatal Intensive Care Unit (NICU) of our hospital from January 2000 to January 2003 were retrospectively studied, 48 of them had TORCH infections. Cytomegalovirus (CMV), rubella and herpes simplex virus infections accounted for 52.1%, 33.3% and 14.6%, respectively. None of them had toxoplasma infection.</p><p><b>CONCLUSION</b>TORCH infections can cause multiorgan lesions, such as hearing impairment, hyperbilirubinemias and liver dysfunction, impairment of neurologic system, myocardial impairment, thrombocytopenia, and congenital heart disease.Rubella vaccine inoculation, serological screening during pregnancy and early period of newborn, intervention and treatment in the early period are most important.</p>

The treatment of molecular adsorbents recirculating system artificial liver in severe liver failure patients with multiple organ dysfunction syndrome / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness and mechanisms of molecular adsorbents recirculating system (MARS) treatment in severe liver failure patients with multiple organ dysfunction syndrome (MODS).</p><p><b>METHODS</b>60 single MARS treatments were performed for 6 - 24 hours on 24 severe liver failure patients with MODS.</p><p><b>RESULTS</b>MARS therapy was associated with marked reduction of albumin bound toxins and water soluble toxins, together with a significant removal of NO and certain cytokines, such as TNF-alpha, IL-6, IL-8, and INF-gamma. These were associated with a improvement of the patients' clinical conditions including hepatic encephalopathy, deranged hemodynamic situation, as well as renal and respiratory function, thus resulted into marked decrease of sequential organ failure assessment (SOFA) score (from 9.72+-1.89 to 6.98+-2.34), and improving outcome: 9 patients were able to be discharged from the hospital or bridged to successful liver transplantation. The overall survival rate of 24 patients was 37.5%.</p><p><b>CONCLUSIONS</b>There is positive therapeutic impact and safety to use MARS on liver failure patients with MODS. The effectiveness of MARS is correlated with reducing the levels of NO and cytokines, except for completely removing of accumulated toxins in liver failure patients.</p>