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Objective: To establish a high performance liquid chromatography-tandem mass spectrometric method ( HPLC-MS/MS) method for the determination of PA-824 in the plasma of Beagle dogs, and study the pharmacokinetics of PA-824 in Beagle dogs. Methods:Carbamazepine was used as the internal standard, and the plasma samples were pretreated with ethyl acetate for the liquid-liquid extraction of PA-824. An Eclipse Plus C18 column (100 mm × 2. 1 mm, 3. 5 μm) was used with the mobile phase consisting of methanol-water (90 :10). The flow rate was 0. 6 ml·min-1 and the column temperature was 30 ℃. The injection volume was 5 μl and the sample analysis time was 5 min. The determination was performed with an electrospray ionization ( ESI) source in the positive multiple reaction monitoring (MRM) mode. The ion pairs were m/z 360. 1→m/z 175. 0 (collision energy of 35, solution cluster volt-age of 65) for PA-824 and m/z 237. 2→m/z 194. 0 (collision energy of 28, solution cluster voltage of 83) for carbamazepine. After the oral administration, PA-824 in plasma was measured at different time points, and then the pharmacokinetic parameters were calcu-lated by DAS 2. 0 software. Results: PA-824 showed a good linear relationship within the range of 50-10000 ng · ml-1 ( r =0. 9991). The recovery was 97. 7%-105. 1%, and the RSDs of intra-day and inter-day were less than 5. 0%. At three different dosa-ges (100, 200 and 500 mg) of PA-824, AUC0-twere (5735. 18 ± 1918. 76),(11548. 47 ± 1838. 04) and (21987. 88 ± 4587. 58) ng·min·ml-1,t1/2 were(14.17 ±5.97),(11.11 ±4.39) and (13.13 ±5.46)h,and Cmaxwere(626.66 ±188.48),(2399.13 ± 516.51) and (4861.33 ±2253.61)ng·ml-1, respectively. Conclusion:The method is simple, accurate, rapid and reproducible, and suitable for the pharmacokinetic study of PA-824 in the plasma of Beagle dogs.
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Objective:To establish an LC-MS/MS method for the simultaneous determination of acetaminophen and its five metabolites in mice plasma,and investigate the metabolism of acetaminophen by using the method.Methods:Para aminobenzoic acid was used as the internal standard.The plasma samples were precipitated by methanol,and then separated on a C18 column with the mobile phase of methanol and 5 mmol·L-1 ammonium acetate buffer solution containing 0.1% formic acid (55∶45).The flow rate was 0.5 ml·min-1,and the column temperature was 25℃.An electrospray ionization source was applied and operated in a positive ion mode using MRM:APAP,-,m/z 152.0→110.0;APAP-cys,-,m/z 271.2→140.1;APAP-glut,-,m/z 457.0→328.0;APAP-NAC,-,m/z 313.4 →208.0;APAP-sulf,-,m/z 232.4→152.1;APAP-gluc,-,m/z 328.2→152.1;IS,-,m/z 138.2→120.0.Results:The method exhibited good linearity over the concentration range of 0.2-10 μg·ml-1for APAP,1.0-20 μg·ml-1 for APAP-gluc,1.0-20 μg·ml-1 for APAP-sulf,1.0-20 μg·ml-1 for APAP-glut,0.4-15 μg·ml-1 for APAP-NAC and 0.2-10 μg·ml-1 for APAP-cys (r≥0.990 0).The inter-day accuracy and precision of acetaminophen and its five metabolites were all below 15%.The average recovery was between 85% and 115%,and RSDs were all below 15%.Conclusion:The LC-MS/MS method is proved to be quick,sensitive and accurate,and suitable for the determination of acetaminophen and its five metabolites in mice plasma.
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Objective To establish a reversed-phase high performance liquid chromatograph ( RP-HPLC ) method for determination of equilibrium solubility and oil/water partition coeficient of phloridzin in different solvents. Methods A RP-HPLC method was established to detect the concentration of phloridzin in water and different organic solvents. The partition coefficients in the n-octanol-water/buffer solution systems of phloridzin were determined by shaking flask method. The Inertsil ODS-3 (4.6 mm×150 mm, 5μm) column was used and the detection wavelength was 284 nm.The flow rate was 1.0 mL??min-1, and acetonitrile-0.05% phosphoric acid(30??70)was used as mobile phase. Results The equilibrium solubility of phloridzin was 2.07 mg??mL-1 in water and 838.63 mg??mL-1 in methanol at 25 ℃.A good linear relationship of phloridzin was obtained within the range of 0.054 9-1.098 0 μg.The regression equation was Y=2 152.9X+7.26 (r=0.999 9).The solubility values of phloridzin were higher in ethanol and propylene glycol than in other solvents. Conclusion RP-HPLC method is simple, quick and accurate for the determination of phloridzin.Phloridzin was almost insoluble in petroleum ether and poorly soluble in water.The equilibrium solubility is higher in methanol than in other solvents. The apparent distribution coefficient of phloridzin varies significantly with pH under the alkaline conditions but less in the acidic solution.
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Objective:To perfect and improve the quality standard of Malloti Apeltae Radix. Methods:Microscopic identification was used to identify the transverse section and the powder. The water-soluble and the fat-soluble components were identified by TLC. Rutin was used as the reference in the characteristic chromatogram established by HPLC to determine the relative retention time and rel-ative peak area of each characteristic absorption band. A SPOLAR C18 chromatographic column ( 250 mm × 4. 6 mm,5μm) was used with acetonitrile-0. 4% phosphate solution as the mobile phase with gradient elution, the detection wavelength was set at 328 nm, the flow rate was 1. 0 ml·min-1, and the temperature was 35℃. Results: The microscopic characteristics were obvious. The spots of TLC were round and clear with good repeatability. Five characteristic absorption bands were shown in the fingerprints with the relative retention time within ± 5% of reference value of rutin, and the relative area of peak 3 and peak 4 was not lower than 0. 23 and 0. 66, respectively. Conclusion:The method is convenient, fast and repeatable, and the result is accurate and reliable, which can be used to control the quality of Malloti Apeltae Radix effectively, and as the main index of the quality standard.
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OBJECTIVE:To discuss the characteristics and regular patterns of adverse drug reactions (ADRs) induced by Qingkailing injection for references of clinical rational drug use. METHODS:ADR cases induced by Qingkailing injection reported in Chinese pharmaceutical journals from 2003 to 2005 were retrieved and analyzed statistically. RESULTS:The ADRs induced by Qingkailing injection were more often seen in men than in women, with children and young adults showing higher percentages. Allergic reactions were the main type of adverse drug reactions. Of the total ADR cases induced by Qingkailing injection, 22 cases(33.33%) were anaphylactic shock,15(22.73%) were allergic reactions,10(15.15%) were allergy of circulation system. CONCLUSION:The ADRs induced by Qingkailing injection may be resulted form many factors, which should be given fully attention in the clinic. ADRs monitoring should be stressed when this drug being used by western medicine physicians to make sure rational use of which and to reduce incidences of ADRs.
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OBJECTIVE:To investigate the situation and characteristics of serious adverse drug reactions (ADR) occurred in our hospital in order to promote rational clinical drug use. METHODS: 25 severe ADR cases collected in our hospital from Jun. 2004 to Dec. 2006 were analyzed statistically and evaluated based on the ADR causality judgment criteria. RESULTS: The 25 severe ADR were associated with 21 kinds of drugs, with anti-infectives (12 kinds) making up the highest proportion, followed by traditional Chinese medicine preparations. The main systems involved in he ADR were skin and its appendages and nervous system. 3 new and severe ADR cases were found to have no report in package inserts or literature. CONCLUSION: Severe ADR may be induced by many factors, therefore, it is necessary to strengthen the awareness of rational drug use to guard against severe ADR and ensure safe and effective medication.