Development and validation of a novel UPLC-MS/MS method for the simultaneous determination of fluticasone propionate and salmeterol in human plasma

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）.

Salmeterol/fluticasone treatment reduces circulating C-reactive protein level in patients with stable chronic obstructive pulmonary disease

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.

Different medications for seasonal allergic rhinitis in adults:A systematic review and meta-analysis

BACKGROUND While the efficacy of medications such as fluticasone furoate(FF),fluticasone propionate(FP),and azelastine-fluticasone(AF)has been substantiated in comparison to their respective placebo controls,uncertainties persist regarding the comparative effectiveness of different intranasal agents.AIM To evaluate the efficacy of FP,FF,and AF in the treatment of adult patients with seasonal allergic rhinitis(SAR)using a meta-analytic approach.METHODS A computer search was conducted in Cochrane Library,PubMed,and EMBASE databases to identify randomized controlled trials assessing the effectiveness and safety of FF,FP,and AF in treating SAR.Data on treatment safety and efficacy were extracted and analyzed through meta-analysis.RESULTS A total of 20 studies were included,comprising 10590 participants.The results of the direct meta-analysis indicated that,compared to placebo,both relative Total Nasal Symptom Score(rTNSS)and relative Total Ocular Symptom Score(rTOSS)significantly decreased post-intervention[mean difference(MD)=-1.48,95%confidence interval(CI):-1.73 to-1.22;MD=-0.66,95%CI:-0.82 to-0.49],with similar findings observed across the FF,FP,and AF subgroups.The network meta-analysis results showed that for improving rTNSS and rTOSS,the SUCRA values ranking from highest to lowest were AF,FP,FF,and placebo.Improvements in rTNSS and rTOSS with FP,FF,and AF were all significantly greater than those observed with placebo,with AF demonstrating superior efficacy compared to both FP and FF.No statistically significant difference in rTNSS improvement was found between FP and FF,although FP exhibited significantly greater improvement in rTOSS compared to FF.CONCLUSION In adult patients with SAR,the combination of azelastine and fluticasone shows a significant effect in improving nasal and ocular symptoms,with FP demonstrating marked improvement in ocular symptoms compared to FF.