Analysis of polymer impurities in ceftazidime raw materials and preparations / 药学学报

To establish a method for the determination of polymer impurities in ceftazidime raw materials and preparations, a ceftazidime degradation solution containing polymer impurities was prepared by forced polymerization. Polymer impurities in the degradation solution were separated and identified by high performance gel chromatography and the column switching-LC-MSn method. A new RP-HPLC method for ceftazidime polymer was established and validated with a Phenomenex Gemini-C18 column using a mobile phase gradient elution of 0.02 mol·L-1 phosphate buffer, methanol and acetonitrile. The results showed that when using this high performance gel chromatography method some small molecular weight impurities were co-eluted with the polymers, resulting in a poor specificity and poor quantitative accuracy. But when using the RP-HPLC method, four polymer impurities were detected in the 25-45 min time range with good specificity, sensitivity and robustness, including two ceftazidime dimers, trimers, and derivatives. Therefore, the described RP-HPLC method is suitable for the quality control of polymer impurities in ceftazidime, and ceftazidime degradation solution can be used as suitable solution for analysis of ceftazidime polymers.

Analysis of polymer impurities in cefixime raw materials and preparations / 药学学报

To establish a method for the determination of polymer impurities in cefixime raw materials and preparations, a cefixime degradation solution containing polymer impurities was prepared by forced polymerization. Polymer impurities in the degradation solution were separated and identified by high performance gel chromatography and the column switching-LC-MSn method. A new RP-HPLC method for cefixime polymer was established and validated with a Phenomenex Gemini-C18 column using a mobile phase gradient elution of 0.5% formic acid-water solution and 0.5% formic acid-acetonitrile solution. The results showed that when using this high performance gel chromatography method some small molecular weight impurities were co-eluted with the polymers, resulting in a poor specificity and poor quantitative accuracy. But when using the RP-HPLC method, three polymer impurities were detected with good specificity, sensitivity and robustness, including two cefixime dimers, and dehydrate dimer. Therefore, the described RP-HPLC method is suitable for the quality control of polymer impurities in cefixime, and cefixime degradation solution can be used as suitable solution for analysis of cefixime polymers.

Rapid Characterization of Impurity Profiles in Vancomycin Raw Material by Column-Switching LC/MSn / 中国药学杂志

OBJECTIVE: To characterize the impurity structures in vancomycin raw material. METHODS: Impurities were eluted gradiently on a Chromasil 100-5 C18(4.6 mm×250 mm, 5 μm) column, with triethylamine buffer solution (pH 3.2)-acetonitrile-tetrahydrofuran (92∶7∶1, V/V/V) as mobile phase A, and triethylamine buffer solution (pH 3.2)-acetonitrile-tetrahydrofuran (70∶29∶1, V/V/V) as mobile phase B. Stress tests were performed on the raw material to specify those impurities. By application of on-line LC/MSn method, the impurities were analyzed in positive mode and their structures were characterized based on the degradation mechanism and mass fragmentation regularity of sugar-lipopeptides. RESULTS: Totally 14 impurities were characterized in the raw material, seven of which were reported for the first time. The relationships between the chemical structures and chromatographic behaviors of vancomycin, demethylvancomycin and methylated vancomycin with their two β-isomers were summarized. CONCLUSION: The structures of related impurities in vancomycin raw material can be rapidly identified by on-line LC/MSn method together with stress degradation experiments.

Qualitative and quantitative analyses of Chrysanthemum morifolium ‘Fubaiju’ by LC-MSn and HPLC-UV / 中国药科大学学报

@#A qualitative analytical method of liquid chromatography coupled with mass spectrometry(LC-MSn)was developed for the identification of main constituents in Chrysanthemum morifolium ‘Fubaiju’. High-performance liquid chromatography(HPLC)was developed for the quantification of five active components, including chlorogenic acid(1), luteolin-7-O-β-D-glucopyranoside(2), luteolin-7-O-β-D-glucopyranuronide(3), 3, 5-Di-caffeoylquinic acid(4), and apigenin-7-O-β-D-glucopyranoside(5). A total of 22 compounds, including 13 flavonoids and 9 phenolic acids, were identified based on their retention behaviors, UV profiles and MS fragment information. Furthermore, a validation method with good linearity(r> 0. 999 9), precision, stability, repeatability and recovery was successfully applied for simultaneous determination of five major components in 10 batches of C. morifolium ‘Fubaiju’ by HPLC-UV method. The established method was proved to be a validation strategy for the quality evaluation of C. morifolium ‘Fubaiju’.

Quantification of midazolam/1′-hydroxymidazolam and their pharmacokinetic characteristics in rat brain by microdialysis combined with LC-MS n / 中国药理学通报

Aim To develop a sensitive, rapid and ac-curate LC-MSn method for determination of midazolam/1′-hydroxymidazolam and their pharmacokinetic char-acteristics in rat brain. Methods SD rats received in-travenous injection of midazolam ( 5 mg · kg-1 ) via femoral vein, a probe drug of cytochrome P450 3A. The microdialysis ( MD ) samples in situ brain were collected every 8 mins at 2. 0μl·min-1 in 2. 4 hours. Analytes in brain dialysate were quantified by the pro-posed LC-MSn method. Gradient elution was performed on an Agilent Eclipse Plus-C18 column ( 2 . 1 × 50 mm, 3. 5 μm). The mobile phase consisted of 2 mmol ·L-1 ammonium acetate and acetonitrile. The analyte was detected using electrospray ionization ( ESI ) in multiple reaction monitoring ( MRM) modes. The reac-tion selected ions were 326 . 1/291 . 1 m/z for midazo-lam, 342. 1/324. 1 m/z for 1′-hydroxymidazolam and 285. 1/154. 0 m/z for diazepam as internal standard. Result The linear ranges of midazolam and 1′-hydroxymidazolam were 0 . 78~100 and 0 . 195 ~12 . 5μg·L-1 respectively. The lower limit of quantification was 0 . 2 μg · L-1 . The RSD of intra- and inter-batch precisions was less than 7 %. The RSD of accuracy was from -1 . 34 to -8 %. Conclusion This sensi-tive and rapid LC-MSn method is suitable for determi-nation of midazolam/1′-hydroxymidazolam in rat brain dialysate. MD combined with LC-MSn method may give assistance to deep and further studies of drug metabo-lism and CYP3A enzyme in brain.

Biotransformation and involved CYP450 isomers of bioactive xanthone HM-1 from Halenia elliptica, D. Don in rat liver microsomes / 中国药学杂志

OBJECTIVE: To study the biotransformation of bioactive xanthones 1-hydroxyl-2, 3, 5-trimethoxyxanthone (HM-1) from Halenia elliptica, D. Don and five mostly common CYP450 isoforms involved of the its metabolism in rat liver microsomes (RLMs).

Comparison of the profiles of chlorogenic acids and their derivatives from three Chinese traditional herbs by LC-MSn / 药学学报

To investigate the chlorogenic acids resources in Eucommia ulmoides Olive leaves, Lonicera japonica Thunb. leaves and Houttuynla cordata Thunb. leaves, methanolic extracts of these three materials have been analysed qualitatively for chlorogenic acids and their derivatives by structure-diagnostic LC-MSn. Three monocaffeoylquinic acids (3-CQA, 4-CQA, 5-CQA) were detected. 5-CQA dominated this subgroup in Eucommia ulmoides Olive and Lonicera japonica Thunb. leaves, but 3-CQA and 4-CQA dominated this subgroup of chlorogenic acids in the leaves of Houttuynla cordata Thunb. Caffeoylquinic acid-glycosides were detected for the first time from Eucommia ulmoides leaves. 5-FQA was found in Lonicera japonica Thunb. leaves, and 3-FQA and 4-pCoQA have been identified in Houttuynla cordata Thunb. This is the first report of the chlorogenic acid profile in Houttuynla cordata Thunb. The comparatively unusual profile of caffeoylquinic acids in Houttuynla cordata Thunb. makes it a convenient source of 3-CQA and 4-CQA that are not commercially available.

Determination of the Metabolites of Ranolazine in Rats by LC-MS~n / 中国药房

OBJECTIVE:To determinate the metabolites of ranolazine in rats by LC-MSn.METHODS:Rats were given 80 mg?kg-1 ranolazine by i.g.During 0～24 h after intragastrical administration,the sample of urine was collected and extracted by solid phase column.Extracts were determined by LC-MSn.The mobile phase consisted of acetonitrile,10 mmol?L-1ammonium acetate and glacial acetic acid at a flow rate of 0.5 mL?min-1.Fragmentation ions of ranolazine and its metabolites were determined in positive electrospray ionization by using MS,MS2 and MS3 full scans.RESULTS:Twelve phaseⅠ metabolites (O-demethylation,O-dearylation,hydroxylation,N-dealkylation and amide hydrolysis) and nine phase Ⅱ metabolites(O-glucuronidation and sulfation) were found in the sample.CONCLUSION:Ranolazine is extensively metabolized in rats.