Guaifenesin Research Articles

Metacarpophalangeal joint luxation with joint capsule rupture and bone exposure in a horse

A 300 kg, 11-month-old quarter horse filly was presented with a joint dislocation in the right anterior limb. The animal was attended at the Federal University of Pará (UFPA) Veterinary Hospital in September 2016, where it was reported that the horse was injured on a fence. On clinical examination, the dislocation of the metacarpophalangeal joint with a rupture of the joint capsule and exposure of bone surfaces was observed, however, with no rupture of the extensor and flexor tendons. Surgery was recommended and the patient was anaesthetised with detomidine (Dormiun V; Agener União, São Paulo, Brazil; 0.04 mg/kg), ketamine (Cetamin; Syntec, São Paulo, Brazil; 0.03 mg/kg/h) and guaiacol glyceryl ether (JA Saúde Animal, São Paulo, Brasil, 0.5 ml/kg/h) i.v. The reconstitution of the joint capsule, lateral collateral ligament (LCL) and the other soft tissues around the injury was performed. A chemical arthrodesis was performed, then the tissue approximation and finally the skin suture. Bandages were applied on the wound with hydrophobic cotton and a Robert-Jones dressing. Systemic treatment was performed with enrofloxacin (Zelotril 10%; Agener União, São Paulo, Brazil; 5 mg/kg) i.m., meloxicam (Maxicam 2%; São Paulo, Brasil; 0.6 mg/kg) i.v. during 10 and 20 days, respectively, then replacing the antibiotic with ceftiofur (Cef 50; Agener União, São Paulo, Brasil; 2.2 mg/kg) i.m. for another 22 days. An iodine solution was applied to the joint optimising arthrodesis. After three and a half months, the lesion was entirely healed and with good movement, so the patient was discharged. This case demonstrates that, with adequate treatment and attention, it is possible to recover the patient’s quality of life.

Stability-Indicating Simultaneous Method Development and Validation of Guaifenesin and Dextromethorphan HBr by Reverse-Phase High-Performance Liquid Chromatography

The developed method was validated according to ICH guidelines with respect to specificity, linearity, limits of detection, quantification, accuracy, precision, and robustness. The stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) method is precise; it has been developed for the simultaneous estimation of assay of guaifenesin (GN) and dextromethorphan hydrobromic (HBr) (DN) in drug substance and drug product. The chromatographic separation was done in an isocratic mode using the Syncronus C8 (250 × 4.6 mm, 5 μ particle size) column with mobile phase containing a 10 mM ammonium acetate in water (modulated pH 4.30 with orthophosphoric acid) and acetonitrile in the ratio of 60:40 (% v/v) used for efficient chromatographic separation. The flow rate of the mobile phase was 1 mL/min with ambient column temperature and detection of wavelength at 279 nm; injection volume 10 μL was fixed for achieving good elution of eluents. The retention time for GN was found to 3.46 minutes and DN was found to 7.58 minutes. GN and DN were linear in the concentration range from 357 to 1,428 and 19 to 75 μg/mL, respectively. Regression analysis showed that the r value (correlation coefficient) greater than 0.999 for GN r value was found to be 0.999, GN r value was found to be 0.999, DN r value was found to be 0.999. Limit of detection (LoD) and limit of quantification (LoQ) of GN was found to be 0.151 and 0.904 μg/mL, DN was found to be 0.241 and 0.726 μg/mL. The developed method was validated and found to be accurate, specific, and robust. Both the drugs were subjected to the stress conditions like acidic, basic, oxidative, photolytic, and thermal conditions. The degradation results were found to be satisfactory. In peroxide stress condition, GN was found stable over DN, and DN was found to degrade significantly. The degradation products were well resolved from GN, DN, and their impurities. The peak purity test results confirmed that the GN and DN peak were homogenous and pure in all stress conditions, thus, proving the stability-indicating nature of the method. This method could be applied for the simultaneous estimation of GN and DN in drug substance and drug product.

Voltammetric Determination of Guaifenesin in Pharmaceuticals and Urine Samples Based on Poly(Bromocresol Purple) Modified Glassy Carbon Electrode

Introduction: The electro-oxidation behavior of expectorant drug Guaifenesin (GUF) was studied on poly(bromocresol purple) modified Glassy Carbon Electrode (GCE) by Cyclic Voltammetry (CV) and Differential Pulse Voltammetry (DPV) methods. Materials and Methods: GCE was modified with electropolymerization of Bromocresol Purple (BP) monomer for sensitive determination of GUF with voltammetric methods. The oxidation process of GUF showed irreversible and diffusion controlled behavior. The linearity has been obtained in the range from 1.00 × 10-7 to 2.00 × 10-5 M with the limit of detection 3.658 × 10-9 M for DPV in 0.1 M phosphate buffer solution (PBS) at pH 3.0. Results and Conclusion: Fully validated differential pulse voltammetry was successfully applied for the determination of GUF in pharmaceutical dosage forms and urine samples obtained satisfying results.

A novel pH-sensitive and magnetic starch-based nanocomposite hydrogel as a controlled drug delivery system for wound healing

pH-sensitive magnetic nanocomposite hydrogel was fabricated by the graft copolymerization of itaconic acid onto starch in the presence of Fe3O4 nanoparticles for Guaifenesin (GFN) delivery and wound healing. The structure of the prepared nanocomposite hydrogels was characterized using FTIR, XRD, SEM, AFM, TEM, DLS, EDX and TGA/DTG techniques. The embedment of Fe3O4 nanoparticles into starch-itaconic acid hydrogel network endowed the material with magnetic property. In addition, GFN not only achieved effectively bound to the nanocomposite hydrogel, but also released in a controlled and pH-dependent manner. The application of an external magnetic field could significantly enhance the drug release percentage, so that only about % 54.1 GFN was released within 24 h in pH 7.4 for free Fe3O4- nanocomposite, whereas that was % 90.4 for nanocomposite with % 0.83 Fe3O4 at the same condition. More importantly, the released GFN preserved its bioavailability. Taken together, these hydrogel drug carriers provide a promising platform for magnetically targeted drug delivery as well as a dress for wound healing.

Synthesis of a novel magnetic starch-alginic acid-based biomaterial for drug delivery

The magnetic composite hydrogel was fabricated by the graft copolymerization of itaconic acid (IA) onto starch and Alginic acid in the presence graphene sheets (Gr) and Fe3O4 nanoparticles (Fe3O4@Gr-IA/St-Alg) for Guaifenesin (GFN) delivery and wound healing. The Fe3O4@Gr-IA/St-Alg biomaterial is a hydrogel network endowed the material with magnetic property. In addition, GFN not only achieved effectively bound to the magnetic hydrogel, but also released in a controlled manner. The using external magnetic field has significantly positive influence on the drug release rate. To close, these hydrogel drug carriers offer a favorable platform for magnetically targeted drug delivery as well as a dress for wound healing.

Simultaneous determination of guaifenesin enantiomers and ambroxol HCl using 50-mm chiral column for a negligible environmental impact.

Chiral stationary phases are conveniently used for enantiomeric separation of drugs by liquid chromatography. Consumption of large volumes of hazardous solvents is considered as a common challenge for the sustainability of this technique. To this end, a columnar chromatography has been adopted using 50-mm-length stationary phases. The study comprised five Phenomenex Lux cellulose- and amylose-based columns for the separation of guaifenesin (GUA) enantiomers. In addition, an experimental design was used to optimize the gradient profile for the separation of racemic GUA and ambroxol HCl (AMB) binary mixture. The chromatographic method was achieved using Lux Cellulose-1 (50×4.6mm) as a chiral stationary phase and ethanol/water as a mobile phase with linear gradient elution of 20% to 70% ethanol in 6minutes at a flow rate of 1.0mLmin-1 and UV detection at 270nm. Linearity ranges were found to be 50 to 1000μgmL-1 and 15 to 450μgmL-1 for each GUA enantiomer and AMB, respectively. Environmental, health and safety tool was used to assess and compare greenness of the proposed and reported methods. Short column indeed reduces the environmental impact by decreasing waste by about 60% and utilizing only 1-mL ethanol in the mobile phase. The proposed method is a safer alternative for the simultaneous determination of drugs in their combined pharmaceutical formulation. The method has been validated and compared favorably with a reported one.

Bilinear and trilinear algorithms utilizing full and selected variables for resolution and quantitation of four components with overlapped spectral signals in bulk and syrup dosage form.

Spectrophotometric-assisted chemometric techniques are beneficial for resolving spectral overlapping and are considered comparable to traditional chromatographic methods. In this work, different chemometric approaches were applied for simultaneous determination of Bromhexine HCl (BRHX), Guaifenesin (GUA) and Salbutamol sulphate (SALB) in the presence of Guaiacol (GUAIA), without any prior separation. Two-way and three-way techniques were applied. The resolving power of genetic algorithm (GA-PLS), trilinear partial least square (N-PLS) and multivariate curve resolution (MCR-ALS) were investigated. A set of 17 synthetic samples in the concentration range 10.0-30.0 μg/mL of BRHX, GUA and SALB and 6.0-10.0 μg/mL of GUAIA were used in the construction of the calibration models. Commercially available syrup dosage form was successfully analyzed by the developed methods without interference from formulation additives. The developed models were evaluated through calculation of root mean squared error of prediction (RMSEP), the obtained values were 0.263, 0.419 and 0.342 for BRHX, 0.254, 0.318 and 0.503 for GUA and 0.298, 0.268 and 0.302 for SALB using N-PLS, MCR-ALS and GA-PLS, respectively. The resolving power of the developed models was emphasized through comparison with a reported HPLC method, where no significant difference was found regarding both accuracy and precision.

RP-HPLC-UV method development and validation for simultaneous determination of terbutaline sulphate, ambroxol HCl and guaifenesin in pure and dosage forms

The objective of the present work was to develop and validate a simple, sensitive, rapid and stable reverse-phase high performance liquid chromatography (RP-HPLC) method for a combination of Terbutaline sulphate (TSL), Ambroxol hydrochloride (AML) and Guaifenesin (GFN). The combination of these drugs was analyzed by using Shimadzu LC 2010 CHT high performance liquid chromatography (HPLC). Successful separation was achieved by isocratic elution on a reverse-phase C18 column (sun fire) (250mm, 4.6mm, 5μ), using a mobile phase consisting of buffer: acetonitrile in the ratio 80: 20 (buffer - 0.1% v/v triethyleamine pH-3.0) followed by 1.0mL/min flow rate. The wavelength of detection was at 220nm. The chromatographic retention times were consistent at 3.0, 10.5 and 13.8minutes for TSL, AML and GFN respectively. For these three compounds, the lower limit of detection was 1.0, 1.25, and 1.5μg/mL and lower limit of quantification was 3.3, 4.1 and 5.0μg/mL respectively. The linearity concentrations established for TSL, AML and GFN were 1.0-7.0, 1.5-7.5 and 4.0-14.0μg/mL respectively. The correlation coefficients for all the drugs were found to be greater than 0.999. The relative standard deviation of inter- and intra-day were less than 2.0%. This method provides a necessary tool for quantification of the selected drugs for their assay. The proposed method is simple, accurate, reproducible and applied successfully to analyze three compounds in pure as well dosage form.

Simultaneous Quantification of Chlorpheniramine, Phenylephrine, Guaifenesin in Presence of Preservatives with Detection of Related Substance Guaiacol in their Cough Syrup by RP-HPLC and TLC-Densitometric Methods.

Two sensitive chromatographic methods have been developed, and validated for chlorpheniramine maleate (CM), phenylephrine (PE) and guaifenesin (GF) determination in their mixture and in presence of GF related substance guaiacol (GL) and preservative namely; sodium benzoate (NaB). The first method was based on thin layer chromatographic separation (TLC) followed by densitometric determination of the separated spots. The separation was achieved using silica gel 60 F254 TLC plates and ethyl acetate: methanol: toluene: ammonia (7:1.5:1:0.5, by volume) as a developing system. Densitometric quantification of the three drugs was carried by the reflectance mode at 270 nm. The second method was based on the use of high-performance liquid chromatography with diode array detection, by which the proposed components were separated on a reversed phase C18 analytical column using phosphate buffer pH 2.9 (containing 0.1 g Heptane-1-sulphonic acid sodium salt) and acetonitrile (85:15, v/v) at 0.8 mL/min for 4 minutes then 1 mL/min till end of the run using flow rate online switching technique. Both methods were validated according to the ICH guidelines and successfully applied for the determination of CM, PE, and GF in pure powder and in combined cough syrup without interference from the excipients.

Reverse phase-UPLC method of analysis for simultaneous estimation of Levosalbutamol sulphate, Guaiphenesin and Ambroxol hydrochloride in pharmaceutical cough, cold liquid dosage forms

The three most drug combinations for cough, cold are widely used worldwide now a day. The purpose of the study was to build up an innovative RP-UPLC technique for simultaneous estimation of Levosalbutamol Sulphate (LEV), Guaiphenesin (GUA) and Ambroxol Hydrochloride (AMB) in liquid dosage forms. Chromatography was carried out on UHPLC (WATERS)_SYMMETRY® C18 4.6mm x 1000mm, 3.5µm, (Agilent - Zorbax Eclipse Plus C18 – Rapid Resolution) with an isocratic mobile phase with pH 3.0 composed of buffer, methanol and Acetonitrile (60:20:20) with a flow rate of 0.8mL/min. The detection was carried out with column temperature at 25°C using a UV detector at 276nm. Validation parameters like linearity, specificity, precision, accuracy, limit of detection (LOD), limit of quantification (LOQ), system suitability, Solutions stability and robustness were considered as affirmed in the ICH guidelines. Retention times for LEV, GUA & AMB were 1.07 min, 1.99 min & 3.55 min respectively. The assay of syrups with the relative standard deviation found to be less than 2%. The parameters values were found, and the method was found to be satisfactory. This validated UHPLC method is cost-effective, receptive and precise than other chromatographic methods.

Voltammetric method for simultaneous determination of ascorbic acid, paracetamol and guaifenesin using a sequential experimentation strategy

Cold is a leading cause of school and work absenteeism. Most cold over-the-counter medicines (OTC) contain paracetamol (PA), guaifenesin (GU) and other active ingredients. Ascorbic acid (AS) in pharmaceutical preparations is designed for preventing and treating respiratory viral infections. Thus, we report a robust voltammetric method for simultaneous determination of AS, PA and GU in their effervescent dosage form. The advantages of nanotechnology and chemometrics were combined to enhance the performance of electroanalysis. Fractional factorial design (FrFD) and dual response surface method (DRSM) were sequentially conducted. The method was validated in agreement with ICH guidelines; it showed accuracy over the concentration range of 11.3–108.9, 14.6–140.3, 4.6–43.9 μg ml−1 for AS, PA and GU, respectively. Based on findings, a robust and not time-consuming procedure was applied.

Simultaneous determination of methocarbamol and aspirin in presence of their pharmacopeial-related substances in combined tablets using novel HPLC-DAD method

Objective and Significance: Methocarbamol (MET) and aspirin (ASP) are widely used as a muscle relaxant combination. The USP reports guaifenesin (GUA) and salicylic acid (SAL) as related substances and hydrolytic products of MET and ASP, respectively. This work aimed at developing and validating a simple and sensitive RP-HPLC method for the determination of both drugs as well as their related substances (at their pharmacopeial limits) in their bulk powders, laboratory prepared mixtures, and MET-ASP combined tablets. Methods and Results: Chromatographic separation was achieved in less than 9 min with the required resolution, peak symmetry, and accuracy on C18 column using isocratic elution system of diluted acetic acid (pH 3.2): acetonitrile at the ratio of 79: 21, v/v, at a flow rate of 1 mL/min. Detection was achieved with photodiode array at 233 nm for MET, GUA, and SAL and at 273 nm for ASP. The developed method has been validated as per ICH guidelines and the calibration plots were linear over the concentration ranges of 2–150, 0.4–30, 25–450, and 0.2–27 μg/mL for MET, GUA, ASP, and SAL, respectively. Conclusion: The optimized method proved to be specific, robust and precise for the quality control of the studied drugs in pharmaceutical preparations to ascertain that their related substances are not exceeding the permitted pharmacopeial limits.

HPTLC-Densitometric Method for Determination of Ascorbic Acid, Paracetamol and Guaifenesin in Presence of Their Toxic Impurities.

Ascorbic acid (ASC), paracetamol (PAR) and guaifenesin (GUF) are co-formulated together as analgesic and expectorant effervescent powder. This work describes a selective stability indicating HPTLC-densitometric method which is the first developed stability indicating one for chromatographic separation of the three studied drugs in presence of paracetamol toxic impurity [4-aminophenol (4-AP)] and guaifenesin related substance [impurity, (guaiacol) (GUC)]. The chromatographic separation was carried out on HPTLC 60F254 plates using chloroform-acetone-trifluoroacetic acid (6.5:3.5:0.30, by volume) as a developing system with UV detection at 254 nm. Factors affecting chromatographic separation have been optimized and good separation was obtained between the studied components where (ASC Rf = 0.05, 4-AP Rf = 0.12, GUF Rf = 0.24, PAR Rf = 0.41 and GUC Rf = 0.56). Method validation has been performed according to ICH guidelines and linearity was achieved in the range of 0.4-2.4, 0.4-2.8 and 4-15 μg/band for ASC, PAR and GUF, respectively. In order to evaluate the developed method it was applied for determination of the cited drugs in G.C.Mol® effervescent powder and the obtained results were statistically compared with those obtained by applying the reported HPLC method using Student's t- and F-tests where no significant difference was observed. The developed method has the advantages over the reported HPLC one of being more sensitive and selective which permit its application in quality control analysis of the cited their in presence of drug impurities.

Six Sigma quality approach for HPLC-UV method optimization

We report a robust HPLC-UV method for ascorbic acid (AS), paracetamol (PA) and guaifenesin (GU) based on response surface/tolerance analysis approach to meet Six Sigma quality of the performance of a chromatographic method. Our goals were the bringing specifications into the optimizations and achieving robustness during the development phase. The critical method attributes (CMAs) were resolution between the peak pairs (Rs), the analysis time(T), tailing factor (Tf), number of theoretical plates (N), and back pressure(P).The critical method parameters (CMPs) included a percentage of organic modifier, a flow rate of the mobile phase, and a temperature of column oven. The separation was performed on a CN column, using an isocratic mode with a mixture of 50 mM potassium dihydrogen phosphate buffer adjusted with ortho-phosphoric acid to pH 2.2 as the aqueous component of the mobile phase and methanol in the ratio 85.9:14.1 (v/v) at 1 ml/min flow rate, with UV detector at 275 nm and a column temperature of 45 °C. The method was validated using the accuracy profiles. Finally, the method was applied to pharmaceutical dosage form.

Green chromatographic method for analysis of some anti-cough drugs and their toxic impurities with comparison to conventional methods

Toxic solvents are widely used in chemical laboratories, which are dangerous on health, safety of workers, and environment. Green chemistry established different principles to keep safety of environment, one of these goals is to replace toxic solvents by greener alternatives or by minimizing the used volumes.Paracetamol (PAR), Guaifenesin (GUF), Oxomemazine (OX), and Sodium benzoate (SB) combination is a widely used cough preparation. 4- aminophenol (4-AP) is PAR poisonous impurity and related substance. Guiacol (GUC) is GUF impurity and related substance; its presence may lead to rejection of GUF sample.An eco-friendly HPTLC method was developed to quantify the studied drugs and their impurities. Chromatographic separation was achieved on HPTLC 60F254 plates using ethylacetate: methanol: 0.05 M ammonium chloride buffer (100: 2: 5, by volume) as a mobile phase and scanning at 225 nm. The linear ranges were 0.25–3.50, 0.50–8.00, 0.25–4.00, 0.20–8.00, 0.05–4.00, and 0.25–4.00 µg/band for PAR, GUF, OX and SB, 4-AP, and GUC. Method was successfully applied to available syrup and suppositories. It compared well with the reported method. It can be considered as an alternative green method for previously developed TLC method. Greenness profile of the method proved that it is greener than the reported methods being time and solvents saving.

LIQUID CHROMATOGRAPHY TANDEM-MASS SPECTROMETRY METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ANALYSIS OF PARACETAMOL, GUAIFENESIN, PHENYLEPHRINE HYDROCHLORIDE, CHLORPHENIRAMINE MALEATE, AND AMBROXOL HYDROCHLORIDE IN BULK AND IN TABLET DOSAGE FORM

Objective: The objective is to study liquid chromatography tandem-mass spectrometry (LC/MS/MS) method for simultaneous quantification of paracetamol (PCM), guaifenesin (GUA), phenylephrine hydrochloride (PE), chlorpheniramine maleate (CPM), and ambroxol hydrochloride (AMB) in tablet dosage form developed and validated as per the International Conference on Harmonization Q2 (R1) guideline. Methods: The chromatograms were developed using a gradient mobile phase of WATER:methanol. Flow rate used was to 0.3 ml/min. Quantitation was performed using multiple reaction monitoring (MRM) mode to study parent to product ion transition, for paracetamol. (m/z 152.0 ≥ 110.0), guaifenesin (m/z 199.0 ≥163.0), phenylephrine hydrochloride (m/z 168.0≥ 150.0), chlorpheniramine maleate (m/z 275.0 ≥ 230.0) and ambroxol hydrochloride (m/z 379.0 ≥ 263.8). Results: The retention times were found to be 1.76, 1.81, 1.90, 2.10, and 2.33 min for PCM, GUA, PE, CPM, and AMB, respectively. The linearity of the method was found to be in the concentration range of 10–200 ng/ml for PCM, GUA, PE, CPM, and AMB. Percentage relative standard deviation values for repeatability and intermediate precision studies were below 2%. Conclusion: Developed method was found to be robust, precise, accurate, rapid and can be used to analyze fixed-dose tablet formulation used in the study.

Reversed-Phase High-Performance Liquid Chromatography and High-Performance Thin-layer Liquid Chromatography Methods for Simultaneous Determination of Theophylline, Guaifenesin and Guaifenesin Impurity (Guaiacol) in Their Bulk Powders and in Dosage Form.

Two simple, rapid chromatographic methods were developed for the simultaneous determination of Theophylline (THP), Guaifenesin (GUI) and Guaifenesin impurity namely Guaiacol (GUA). The first method is an isocratic reversed-phase high-performance liquid chromatography (RP-HPLC) method, where separation of THP, GUI and GUA was achieved on C18 column using methanol:water (containing 0.1% triethylamine):acetonitrile (30:60:10, by volume) as a mobile phase with a flow rate of 0.7 mL /min and UV detection at 275 nm. The separation was achieved at retention times (Rt 3.76, 6.76 and 8.79 for THP, GUI and GUA, respectively). The calibration plots were linear over the concentration range of 2-25, 2-37 and 0.5-10 μg /mL for THP, GUI and GUA, respectively. The second method is high pressure thin layer liquid chromatography method, which was developed using silica gel plates 60F254 as a stationary phase with ethyl acetate:hexane:methanol:ammonia (65:35:10:2, by volume) as a developing system. The densitometric measurements were performed at 275 nm with good Rf values (0.13, 0.35 and 0.8) for THP, GUI and GUA, respectively. The calibration plots showed good correlation over the range (0.4-2 μg/band) for both THP and GUI, and (0.4-1.2 μg/band) for GUA. The two proposed methods were validated according to ICH guidelines. The results for the two methods were statistically compared to those obtained by a reported high-performance liquid chromatography method and no significant difference was found regarding accuracy and precision.

Use of continuous wavelet transform approach for simultaneous quantitative determination of multicomponent mixture by UV–Vis spectrophotometry

In the present paper, a multicomponent analysis approach based on spectrophotometry method was developed for simultaneous determination of Guaifenesin (GU), Chlorpheniramine (CHL) and Pseudoephedrine (PSE) without any separation steps. The method under study is signal processing method based on Continuous Wavelet Transform (CWT) coupled with zero cross point technique. In this paper, CWT method was tested by synthetic ternary mixtures and was applied to the commercial cough syrup as a real sample and assessed by applying the standard addition technique. For demonstrate the accuracy of the results, other applications of signal processing, such as Derivative Transform (DT), Partial Least Squares (PLS) regression and Principal Components Regression (PCR) were used as comparative methods. Afterwards, the obtained results from analyzing the cough syrup by all methods were compared to the High-Performance Liquid Chromatography (HPLC) as a reference method. One-way analysis of variance test at 95% confidence level showed no significant differences between CWT and other applications.

DEVELOPMENT AND VALIDATION OF DOUBLE DIVISOR RATIO SPECTRA DERIVATIVE SPECTROPHOTOMETRY METHOD FOR TERNARY MIXTURE OF GUAIFENESIN, DEXTROMETHORPHAN HBR, AND DIPHENHYDRAMINE HCL IN TABLET DOSAGE FORM

Objective: This study aimed to develop spectrophotometry method by double divisor ratio spectra derivative to determine the levels of guaifenesin (GUA), dextromethorphan hydrobromide (DMP), and diphenhydramine hydrochloride (DPH) in tablet dosage form using ethanol as solvent.Methods: The method is based on the use of the coincident spectra of the derivative of the ratio spectra obtained using a double divisor (sum of two spectra) and measuring at either the maximum or minimum wavelengths. Then, the method was applied to determine the levels of GUA, DMP, and DPH in tablet dosage form.Results: The application of double divisor ratio spectra derivative spectrophotometry method for the determination of GUA, DMP, and DPH was performed on the first derivative at Δλ 2 (λ 280.0 nm, λ 286.1 nm, and 260.2 nm, respectively). The selection of wavelengths based on wavelengths gives the best result. The mean % recoveries were found to be in 100.60%, 99.95%, and 101.74% for GUA, DMP, and DPH, respectively.Conclusion: The method is successfully applied to analyze GUA, DMP, and DPH in pharmaceutical formulation with no interference from excipients as indicated by the recovery study. All validation parameters were within the acceptable range.

Validated UPLC method for the determination of guaiphenesin, oxeladin citrate, diphenhydramine, and sodium benzoate in their quaternary mixture used in treatment of cough, in the presence of guaiphenesin-related substance (guaiacol)

Accurate, precise, and sensitive UPLC method was developed and validated for the simultaneous determination of a quaternary mixture containing guaiphenesin (GUP), oxeladin citrate (OXC), diphenhydramine (DPH), and sodium benzoate (SOB) in the presence of GUP-related substance, guaiacol (GUA). Chromatographic separation was achieved using NUCLEOSHELL® column—C18 (4.0 × 50.0 mm, 2.7 μm). Isocratic elution at a flow rate 1.0 mL/min was performed using a mobile phase consisting of acetonitrile:phosphate buffer pH 3.5 ± 0.1 (25.0:75.0, v/v). The specificity of the developed method was investigated by analyzing of laboratory-prepared mixtures containing different ratios of the four drugs, in the presence of GUA as well as their combined pharmaceutical formulation. The obtained results were statistically compared with those obtained by the official or reported methods, showing no significant difference with respect to accuracy and precision at p = 0.05.