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A novel, simple and sensitive spectrofluorimetric approach for determination of terbutaline sulphate (TER) and its prodrug bambuterol (BAM) in their pure and pharmaceutical dosage forms was developed. The suggested approach depends on enhancing the native fluorescence of either TER or BAM at 315 and 297.2 nm after excitation at 277 and 259 nm, respectively, using sodium dodecyl sulphate (SDS) as a micellar medium. In the presence of 0.7% w/v SDS, ~1.38-fold and 1.18-fold enhancement is achieved in the relative fluorescence intensity (RFI) of TER and BAM, respectively. The fluorescence-concentration curves were rectilinear over the concentration range 0.8-16 µg ml-1 , with detection limits (LOD) of 0.252 and 0.26 (µg ml-1 ), quantitation limits (LOQ) of 0.76 and 0.79 (µg ml-1 ), determination coefficients (r2) of 0.9981, and slopes of 45.92 and 10.44 for TER and BAM, respectively. The suggested approach was validated in accordance with International Council for Harmonisation criteria and was effectively applied in the analysis of the studied drugs in their commercial tablets. The high sensitivity of the proposed approach allows its application in evaluating the content uniformity testing of the studied drugs in their tablets through using the official United States Pharmacopeia criteria. Statistical analogies of the findings with that of the reported methods showed really good harmony and indicated no major differences in precision and accuracy.
Assuntos
Micelas , Pró-Fármacos , Broncodilatadores , Limite de Detecção , Espectrometria de Fluorescência/métodos , Comprimidos/análise , Terbutalina/análogos & derivadosRESUMO
OBJECTIVE：To study the mecha nism of Bambuterol hydrochloride in the improvement of chronic obstructive pulmonary disease （COPD）model rats ，and to find the potential biomarker. METHODS ：Totally 30 rats were randomly divided into normal group ，model group and bambuterol hydrochloride group （3.3 mg/kg），with 10 rats in each group ；COPD model was established by lipopolysaccharide （LPS）infusion combined with smoking in model group and bambuterol hydrochloride group. After modeling ，bambuterol hydrochloride group was given relevant medicine intragastrically ，normal group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 45 d. After last medication ，the serum sample and alveolar lavage fluid of rats were collected. The levels of interleukin- 6（IL-6）and tumor necrosis factor-α（TNF-α）in alveolar lavage fluid were detected by ELISA. The serum metabolites were detected by LC-MS and analyzed by metabolomics. Orthogonal partial least squares discriminant analysis （OPLS-DA）was used to screen out the differential metabolites. The potential biomarkers were identified based on the related literature ，and the metabolic pathway enrichment analysis was carried out by MetPA analysis platform. RESULTS ：Compared with normal group ，the levels of IL- 6 and TNF-α in alveolar lavage fluid of rats were increased significantly in model group （P＜0.05）. Compared with model group ，the levels of IL- 6 and TNF-α in alveolar lavage fluid of rats were decreased significantly in bambuterol hydrochloride group （P＜0.05）. Results of metabolomics and OPLS-DA showed that 21 differential metabolites and 12 potential biomarkers were found （including maleylpyruvate ， hydroxypyruvate， tartronate semialdehyde，etc.）. Bambuterol hydrochloride can significantly reduce the levels of maleylpyruvate ，methylselenocysteine and 5-deoxy-D-glucuronic acid （P＜0.05）， while increase the levels of hydroxypyruvate ， tartronate semialdehyde and. These biomarkers were mainly @163.com concentrated in pentose phosphoric acid pathway ，glyoxyli acid and tricarboxylic acid metabolism pathway ，followed by 开发。E-mail：pn333@163.com inositol phosphoric acid metabolism pathway ，arginine and tyrosine metabolism pathway ，glycine，serine and threonine metabolism pathway. CONCLUSIONS ：The mechanism of bambuterol hydrochloride improving COPD may be associated with the decrease of the levels of TNF-α and IL-6，as well as the pathway of amino acid metabolism ，energy metabolism and lipid metabolism.
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Objective: To establish a rapid and accurate method for the determination of 15 chemical drugs which were illegally added into the slimming Chinese patent medicines (CPM) and health foods. Methods: The UPLC-MS/MS method was adopted. The samples were extracted with methanol by ultrasonic processing and separated on a Waters Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with 0.1% formic acid methanol (A) -0.1% formic acid water (B) as mobile phase by gradient elution (0-3 min, 33%-45% A; 3-5 min, 45%-55% A; 5-7 min, 55%-70% A; 7-9 min, 70%-80% A; 9-10 min, 80%-90% A; 10-11 min, 90%-33% A; 11-13 min, 33% A at a flow rate of 0.2 mL/min, and the column temperature was 40℃. A positive-ion (ESI+) source and an MRM mode were used to separate and quantitatively determine 15 chemical drugs. The obtained molecular ions, fragment ions, and retention time for MRM channels were used to identify the 15 kinds of drugs by comparison with those of reference substances. The obtained peak areas were used to determine the accurate contents of chemical drugs in CPM and the health foods. Results: A good resolution of 15 kinds of chemical drugs, including terbutaline hydrochloride, ephedrine hydrochloride, theophylline, caffeine, doxofylline, clenbuterol hydrochloride, tulobuterol hydrochloride, bambuterol hydrochloride, fenfluramine hydrochloride, furosemide, indapamide, phenolphthalein, sibutramine hydrochloride, N-demethylated sibutramine hydrochloride, and hydrochloric acid N,N-dinor sibutraminel, was obtained under this UPLC and MS/MS condition. The limits of qualitation and quantitation were in the range of 0.1-5.0 ng/g and 0.3-15.0 ng/g. The standard addition recoveries were in the range of 91.8%-110.8%. In the 86 batches of samples (including capsules, granules, and other different matrix types) were detected in the 74 batches of added chemicals, the positive rate was 86.0%. Sibutramine hydrochloride (39 batches), furosemide (20 batches), phenolphthalein (23 batches), theophylline (1 batch), and caffeine (15 batches) were checked out in the samples, 22 batches of which two kinds were checked out, one batch of which three kinds were checked out. By contrast, the products which were not clearly marked manufacturer illegally added more seriously. Conclusion: The method is simple, accurate, and highly sensitive, which can be used for the determination of illegally added chemical drugs in slimming CPM and health foods.
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A rapid, simple, sensitive and selective analytical method was developed by using reverse phase ultra performance liquid chromatographic technique for the simultaneous estimation of bambuterol hydrochloride and montelukast sodium in combined tablet dosage form. The developed method is superior in technology to conventional high performance liquid chromatography with respect to speed, resolution, solvent consumption, time, and cost of analysis. Elution time for the separation was 6 min and ultra violet detection was carried out at 210 nm. Efficient separation was achieved on BEH C18 sub-2-µm Acquity UPLC column using 0.025% (v/v) trifluoro acetic acid in water and acetonitrile as organic solvent in a linear gradient program. Resolutions between bambuterol hydrochloride and montelukast sodium were found to be more than 31. The active pharmaceutical ingredient was extracted from tablet dosage from using a mixture of methanol, acetonitrile and water as diluent. The calibration graphs were linear for bambuterol hydrochloride and montelukast sodium in the range of 6.25-37.5 µg/ml. The percentage recoveries for bambuterol hydrochloride and montelukast sodium were found to be in the range of 99.1-100.0% and 98.0-101.6%, respectively. The test solution was found to be stable for 7 days when stored in the refrigerator between 2-8°. Developed UPLC method was validated as per International Conference on Harmonization specifications for method validation. This method can be successfully employed for simultaneous estimation of bambuterol hydrochloride and montelukast sodium in bulk drugs and formulations.
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An accurate, specific and precise assay level gradient reverse-phase high-performance liquid chromatographic method was developed for simultaneous determination of montelukast sodium and bambuterol hydrochloride in tablet dosage form. An inertsil ODS C-18, 5 mum column having 250x4.6 mm I.D. in gradient mode, with mobile phase A, containing 0.025 M sodium phosphate buffer: methanol (85:15) and mobile phase B, containing acetonitrile:methanol (85:15) was used at different time intervals. The flow rate was 1.5 ml/min and effluent was monitored at 218 nm. The retention times of montelukast sodium and bambuterol hydrochloride were 21.2 min and 5.8 min respectively. The linearity for both the drugs was in the range of 0.25-0.75 mg/ml with correlation coefficients of 0.9999 and 0.9996 for montelukast sodium and bambuterol hydrochloride, respectively.
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Objective To evaluate the efficacy and safety of oral liquid of bambuterol hydrochloride in treatment children with asthma. Methods One hundred and fifty cases as study group treated with oral liquid of bambuterol hydrochloride,50.cases as control group treated with etinoline. Results Two groups had good efficacy, however, gasp and lung wheezing were better improved in study group compared with control group after 1 week treatment(P
