Combined administration of fluticasone propionate and salmeterol xinofoate has been widely used for the treatment of asthma in recent decades. In this investigation, we developed and validated a novel and sensitive ul...Combined administration of fluticasone propionate and salmeterol xinofoate has been widely used for the treatment of asthma in recent decades. In this investigation, we developed and validated a novel and sensitive ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for simultaneous determination of fluticasone propionate and salmeterol xinofoate in human plasma. Following a simple SPE sample extraction in 96-well plate format, chromatography was performed on a Waters ACQUITY UPLC BEH C 18 column （1.7 μm, 50 min×2.1 mm） with mobile phase consisting of 100% MeOH and 0.1% NH4OH in water on a gradient program at flow rate of 0.5 mL/min. Detection of analytes and internal standards was accomplished using multiple reaction monitoring （MRM） of precursor〉product ion pairs of m/z 501.4〉313.2 （fluticasone propionate）, 506.4〉293.3 （fluticasone propionate-d5）, 416.4〉232.1 （salmeterol xinofoate） and 419.3〉235.2 （salmeterol-d3）. The assay range was 2.50-500 pg/mL for both analytes, and a 1/x2 weighted linear regression model was used. The inter-assay accuracy and precision of the method were within ±8.6%. The recoveries from 0.30 mL of plasma were greater than 51.0% and 54.6% for fluticasone propionate and salmeterol, respectively, and the results were consistent across low, middle and high concentration levels. The method was validated following FDA, EMA and CFDA （China Food and Drug Administration）＇s guidance on bioanalysis and then successfully applied to support a clinical study in healthy Chinese subjects following inhaled administration of a single combination of fluticasone propionate/salmeterol （250 μg/50 μg）.展开更多
Background Evidence suggests that systemic inflammation may play an important role in the progression and morbidity of chronic obstructive pulmonary disease. It remains controversial whether inhaled corticosteroid in ...Background Evidence suggests that systemic inflammation may play an important role in the progression and morbidity of chronic obstructive pulmonary disease. It remains controversial whether inhaled corticosteroid in combination with a long-acting 132-adrenoceptor agonist can attenuate systemic inflammation. We evaluated the effect of salmeterol/fluticasone propionate on circulating C-reactive protein level in stable chronic obstructive pulmonary disease patients. Methods An open-label clinical trial was conducted to recruit 122 outpatients with stable moderate-to-severe chronic obstructive pulmonary disease from department of respiratory medicine in two teaching hospitals between June 2007 and March 2008. Patients were randomized into two groups （1：1） to receive either the combination of 50 μg salmeterol and 500 μg fluticasone twice daily （n=61）, or the combination of 206 μg albuterol and 36 pg ipratropium q.i.d （n=61） over 6 months. Circulating C-reactive protein concentrations were measured before randomization and during the follow-up. The efficacy of treatment was also assessed by spirometry, as well as health status and dyspnea score at baseline and after 6-month treatment. Results Baseline characteristics of two groups were similar. Compared with ipratropium/albuterol, the combination of salmeterol/fluticasone significantly reduced circulating level of C-reactive protein （-1.73 vs. 0.08 mg/L, respectively, P 〈0.05） after 6-month treatment. Forced expiratory volume in one second （FEV1） and health status also improved significantly in salmeterol/fluticasone group compared with ipratropium/albuterol. Salmeterol/fluticasone treatment subjects who had a decrease of circulating C-reactive protein level had a significant improvement in FEV1 and St George＇s Respiratory Questionnaire total scores compared with those who did not （185 vs. 83 ml and -5.71 vs. -1.79 units, respectively, both P 〈0.01）. Conclusion Salmeterol/fluticasone treatment reduced circulating C-reactive protein concentration in clinically stable moderate-to-severe chronic obstructive pulmonary disease patients after 6-month treatment.展开更多
文摘Combined administration of fluticasone propionate and salmeterol xinofoate has been widely used for the treatment of asthma in recent decades. In this investigation, we developed and validated a novel and sensitive ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for simultaneous determination of fluticasone propionate and salmeterol xinofoate in human plasma. Following a simple SPE sample extraction in 96-well plate format, chromatography was performed on a Waters ACQUITY UPLC BEH C 18 column （1.7 μm, 50 min×2.1 mm） with mobile phase consisting of 100% MeOH and 0.1% NH4OH in water on a gradient program at flow rate of 0.5 mL/min. Detection of analytes and internal standards was accomplished using multiple reaction monitoring （MRM） of precursor〉product ion pairs of m/z 501.4〉313.2 （fluticasone propionate）, 506.4〉293.3 （fluticasone propionate-d5）, 416.4〉232.1 （salmeterol xinofoate） and 419.3〉235.2 （salmeterol-d3）. The assay range was 2.50-500 pg/mL for both analytes, and a 1/x2 weighted linear regression model was used. The inter-assay accuracy and precision of the method were within ±8.6%. The recoveries from 0.30 mL of plasma were greater than 51.0% and 54.6% for fluticasone propionate and salmeterol, respectively, and the results were consistent across low, middle and high concentration levels. The method was validated following FDA, EMA and CFDA （China Food and Drug Administration）＇s guidance on bioanalysis and then successfully applied to support a clinical study in healthy Chinese subjects following inhaled administration of a single combination of fluticasone propionate/salmeterol （250 μg/50 μg）.
文摘Background Evidence suggests that systemic inflammation may play an important role in the progression and morbidity of chronic obstructive pulmonary disease. It remains controversial whether inhaled corticosteroid in combination with a long-acting 132-adrenoceptor agonist can attenuate systemic inflammation. We evaluated the effect of salmeterol/fluticasone propionate on circulating C-reactive protein level in stable chronic obstructive pulmonary disease patients. Methods An open-label clinical trial was conducted to recruit 122 outpatients with stable moderate-to-severe chronic obstructive pulmonary disease from department of respiratory medicine in two teaching hospitals between June 2007 and March 2008. Patients were randomized into two groups （1：1） to receive either the combination of 50 μg salmeterol and 500 μg fluticasone twice daily （n=61）, or the combination of 206 μg albuterol and 36 pg ipratropium q.i.d （n=61） over 6 months. Circulating C-reactive protein concentrations were measured before randomization and during the follow-up. The efficacy of treatment was also assessed by spirometry, as well as health status and dyspnea score at baseline and after 6-month treatment. Results Baseline characteristics of two groups were similar. Compared with ipratropium/albuterol, the combination of salmeterol/fluticasone significantly reduced circulating level of C-reactive protein （-1.73 vs. 0.08 mg/L, respectively, P 〈0.05） after 6-month treatment. Forced expiratory volume in one second （FEV1） and health status also improved significantly in salmeterol/fluticasone group compared with ipratropium/albuterol. Salmeterol/fluticasone treatment subjects who had a decrease of circulating C-reactive protein level had a significant improvement in FEV1 and St George＇s Respiratory Questionnaire total scores compared with those who did not （185 vs. 83 ml and -5.71 vs. -1.79 units, respectively, both P 〈0.01）. Conclusion Salmeterol/fluticasone treatment reduced circulating C-reactive protein concentration in clinically stable moderate-to-severe chronic obstructive pulmonary disease patients after 6-month treatment.
