Novel Approach for the Simultaneous Determination of Carbinoxamine Maleate, Pholcodine, and Ephedrine Hydrochloride Without Interference from Coloring Matter in an Antitussive Preparation Using Smart Spectrophotometric Methods

Abstract

The presence of coloring matters in syrups usually interferes with the spectrophotometric determination of active pharmaceutical ingredients. A novel approach was introduced to eliminate the interference of sunset yellow (coloring matter) in Cyrinol syrup. Smart, simple, accurate, and selective spectrophotometric methods were developed and validated for the simultaneous determination of a ternary mixture of carbinoxamine maleate, pholcodine, and ephedrine hydrochloride in syrup. Four of the applied methods used ratio spectra: successive derivative subtraction coupled with constant multiplication, successive derivative of ratio spectra, ratio subtraction coupled with ratio difference, and ratio spectra continuous wavelet transforms zero-crossing. In addition, a method that was based on the presence of an isosbestic point, the amplitude summation method, was also established. A major advantage of the proposed methods is the simultaneous determination of the mentioned drugs without prior separation steps. These methods were successfully applied for the determination of laboratory-prepared mixtures and a commercial pharmaceutical preparation without interference from additives, thus proving the selectivity of the methods. No significant difference regarding both accuracy and precision was observed upon statistical comparison of the results obtained by the proposed methods with each other and with those of official or reported ones.

Determination of pholcodine alone or in combination with ephedrine in human plasma using fluorescence spectroscopy

“…It is reported that PHL and EPH are formulated alone or with other drugs in a syrup formulation. The obtained results and those attained using a comparison method 9 (Supplementary Table S1 ) did not differ significantly (Table 5 ). Statistical evaluation of the results adopting Student's t-test and Variance Ratio F-test 50 indicated that the two approaches performed similarly regarding accuracy and precision, respectively.…”

“…Variable methods for determination of PHL have been reported including UV/Vis spectrophotometry 9 , spectrofluorimetry 10 , high-performance liquid chromatography (HPLC) 11 – 14 , gas chromatography (GC) 15 , chemiluminescence 16 , non-aqueous titration 17 , and electrochemistry 5 , 18 . Similarly, EPH was determined using spectrophotometric methods 19 – 22 , HPLC 23 – 25 , capillary electrophoresis 26 – 29 , GC 30 , 31 , LC-MS 30 , 32 , 33 , and electrochemistry 34 , 35 .…”

“…Similarly, EPH was determined using spectrophotometric methods 19 – 22 , HPLC 23 – 25 , capillary electrophoresis 26 – 29 , GC 30 , 31 , LC-MS 30 , 32 , 33 , and electrochemistry 34 , 35 . While the methods reported for the simultaneous quantitation of PHL and EPH mixture were spectrophotometric 9 , HPLC 8 , 36 , and TLC methods 8 .…”

Paper-based potentiometric sensing devices modified with chemically reduced graphene oxide (CRGO) for trace level determination of pholcodine (opiate derivative drug)

“…So, it appears to be devoid of addiction liability in man. 4 Different analytical methods were reported for the determination of pholcodine including non-aqueous titration, 5 chemiluminescence, 4,6 UV/Vis spectrophotometry, 7 capillary gas chromatography (GC), 8,9 GC-mass spectrometry (MS), 10,11 highperformance liquid chromatography (HPLC), [12][13][14][15][16] ultraperformance liquid chromatography (UPLC)-MS/MS, 17 thinlayer chromatography, 18 capillary electrophoresis (CE), 19 electrochemistry 20 and 1HNMR-pH titration. 21 The use of electrochemical sensors and especially potentiometric sensors has become greatly expanded and now occupies a large part in different applications such as pharmaceutical, environmental and biomedical analysis.…”

Quantitative Determination of Ephedrine Hydrochloride in Pharmaceutical Injections by Highly Sensitive Turbidimetric and Reversed-Phase Combined with UFLC Methods

“…Therefore, developing simple and accurate methods is necessary for the detection and separation of this compound from the pharmaceutical preparations for the routine control analysis. In the literature, several quantitative methods have been presented for the determination of ephedrine in pharmaceutical preparations, including titration technique, which is frequently used to determine pure ephedrine hydrochloride in tablets, aqueous and non-aqueous solutions [6], ratio spectra derivative spectrophotometric [7][8][9], differential-derivative spectroscopic methods [10,11], two dimensional-IR [12], capillary electrophoresis [13] and liquid chromatographic analysis (LC) [14,15].…”