Simultaneous determination of paracetamol, dextromethorphan, chlorpheniramine, pseudoephedrine and major impurities of paracetamol and pseudoephedrine by using capillary electrophoresis

Abstract A capillary electrophoresis method was developed for the first time and optimized for the determination of paracetamol, pseudoephedrine, dextromethorphan, chlorpheniramine, 4-aminophenol and ephedrine in tablet formulation. Optimum electrophoretic conditions were achieved by using a background electrolyte of 75 mmol L-1 sodium borate buffer at pH 8.0, a capillary temperature of 30°C, a separation voltage of 30 kV and a pressure injection of the sample at 50 mbar for 10 s. Calibration graphs showed a good linearity with a coefficient of determination (R2) of at least 0.999 for all compounds. Intraday and interday precision (expressed as relative standard deviation (RSD) %) were lower than 1.39% for capillary electrophoresis method. The developed method was demonstrated to be simple and rapid for the determination of paracetamol, pseudoephedrine, dextromethorphan, chlorpheniramine, 4-aminophenol and ephedrine in tablet formulation providing recoveries in the range between 99.62 and 100.57% for all analytes.

Enhanced histamine H1 receptor blockade with chlorpheniramine in the asthmatic tracheo-bronchial tree: further evidence for increased drug delivery in asthma

We have measured the competitive antagonistic effect of chlorpheniramine in bronchi of 8 normal and 12 asthmatic subjects. Classical pharmacological theory states that the degree of competitive antagonism depends only upon 1] antagonist concentration at the receptor, and 2] receptor affinity. Delivery and affinity also influence agonist responsiveness, but measurement of bronchial antagonism allows study of these factors in isolation. Bronchial responsiveness to histamine was measured as the dose required to produce a 35% fall in specific conductance [sGaw], called PD [35] On different days, 2 measurements of control PD[35] were made on each subject. Measurements of PD[35] were also repeated after inhalation of 1.45 mg chlorpheniramine and intravenous injection of 0.17 mg/kg chlorpheniramine. Antagonist effect of chlorpheniramine was measured as Dose Ratio-1 [DR-1], where DR= PD [35] after chlorpheniramine/control PD[35] Geometric mean of DR-I with inhaled chlorpheniramine in asthmatic subjects [5.8] was 6.8 times that of normal subjects [0.86] [p=0.002], and DR-1 with intravenous chlorpheniramine in asthmatic subjects [4.4] was 2.75 times that of normal subjects [1.6] [p=0.005]. There were significant negative correlations between PD[35] and DR-1, whether chlorpheniramine was administered by inhalation [r= -0.87, p<0.001] or intravenously [r= -0.62, p<0.005]. There was also a significant correlation between DR-I obtained by two routes of administration [r= 0.77, p<0.001]. Taken with our previous study showing enhanced antagonism with atropine at bronchial muscarinic receptors in asthma, these results suggest that drug delivery by inhaled and parenteral routes may be increased in asthmatic bronchi