Two green and sensitive spectrofluorimetric approaches for determination of Ambroxol and guaifenesin in their single and combined pharmaceutical formulations.

Ambroxol hydrochloride (AMX) and guaifenesin (GFN) are approved drugs utilized to treat coughs through their potent mucolytic and expectorant properties. Due to their massive, combined administration in many illnesses, there is a persistent need for their concurrent estimation in different pharmaceutical formulations. Two sensitive, environmentally friendly spectrofluorimetric methods were developed. AMX was determined using the first method (I) without interference from GFN. This method depends on the quenching of Erythrosine B (EB) native fluorescence at 552 nm after excitation at 527 nm due to the formation of a non-fluorescent AMX-EB ion-pair complex in Britton-Robinson buffer (BRB) solution pH (3.5). The concentration plot is linear over the 0.25-5.0 µg/mL range, with a mean percent found value of 99.74%. Method (II) depends on measuring the native fluorescence of aqueous GFN solution at two analytical wavelengths, either 300 or 600 nm, after excitation at 274 nm. Relative fluorescence intensity (RFI)-concentration plots are linear over the ranges of 0.02-0.5 and 0.1-2.0 µg/ml, with mean percent found at 99.96% and 99.91% at dual wavelengths, respectively. The proposed methods were successfully applied to assay both drugs in raw materials and different single and combined pharmaceutical formulations. These methods have been thoroughly validated following International Committee on Harmonisation (ICH) guidelines. National Environmental Methods Index, Analytical Eco-Scale, and Green Analytical Procedure Index were used to prove greenness, thereby enhancing their applicability. The proposed techniques provide straightforward, precise, and cost-effective solutions for routine formulation analysis in quality control laboratories.

A Chemometric Strategy in the Development of a RP-UPLC Method for the Quantitative Resolution of a Two-Component Syrup Formulation.

A novel chemometric strategy was implemented in the development of a new ultraperformance liquid chromatography method for the quantitative estimation of guaifenesin and pseudoephedrine hydrochloride in a two-component syrup formulation with minimal experimental effort, time and reagent. A full factorial design with three factors was investigated to find optimal working conditions of chromatographic factors (column temperature, flow rate, and 0.1 M H3PO4% in mobile phase) that affect the chromatographic separation. Then, optimum experimental conditions providing adequate separation of the analyzed drug substances within the short runtime were determined. Under optimal experimental conditions, the retention times for guaifenesin and pseudoephedrine hydrochloride were obtained as 0.817 and 1.430 min, respectively. In the optimized RP-UPLC method, chromatographic response was reported as a linear function of concentration between 5.0 and 80.0 µg/mL for guaifenesin and 10.0-90.0 µg/mL for pseudoephedrine hydrochloride. The proposed method was carefully validated and successfully applied to quality control and analysis of a cough syrup preparation containing guaifenesin and pseudoephedrine hydrochloride. Consequently, the proposed reversed-phase ultraperformance liquid chromatography method provided an opportunity to quantify relevant drugs with small amount of reagents and short runtime.

High-Performance Liquid Chromatography Method for Simultaneous Determination of Guaifenesin, Salbutamol Sulfate and Guaifenesin Impurity (Guaiacol).

A simple and reliable HPLC method is developed for isocratic separation of a ternary mixture of Salbutamol Sulfate (SAL), Guaifenesin (GUI) and its impurity Guaiacol (GUA) either in pure powder or in pharmaceutical formulation. Chromatographic separation was applied on a Hypersil GOLD CN column with a mobile phase consisting of 0.05 M KH2PO4 (containing 0.1% triethylamine, pH adjusted to 3.7 by phosphoric acid): methanol (60: 40 by volume) using 0.6 mL min-1 flow rate and detection of peaks at 275 nm at 25°C with run time around 6 min. The calibration plots were linear over the concentration ranges of 0.5-20, 0.5-30 and 0.1-10 µg mL-1 for SAL, GUI and GUA, respectively. ICH guidelines were used for the validation of presented method. The obtained results were compared with the results obtained from the reported HPLC method and no significant difference was found regarding accuracy and precision.

Electroanalytical Analysis of Guaifenesin on Poly(Acridine Orange) Modified Glassy Carbon Electrode and its Determination in Pharmaceuticals and Serum Samples.

BACKGROUND: Electroanalytical methods are very functional to detect drugs in pharmaceuticals (tablets, syrups, suppositories, creams, and ointments) and biological samples. OBJECTIVE: This study is aimed to make selective, sensitive, simple, fast, and low cost electrochemical analysis of expectorant drug guaifenesin in pharmaceuticals and serum samples. METHODS: Differential pulse adsorptive stripping voltammetric method for determination of guaifenesin on a poly(acridine orange) modified glassy carbon electrode has been developed. Glassy carbon electrode was modified with electropolymerization of the acridine orange monomer for the sensitive determination of guaifenesin. Guaifenesin provided highly reproducible and welldefined irreversible oxidation peaks at +1.125 V and +1.128 V (vs. Ag/AgCl) in the selected supporting electrolyte and human serum samples, respectively. RESULTS: Under optimized conditions, linear response of peak current on the concentration of guaifenesin has been obtained in the ranges of 2.00×10-7 to 1.00×10-4 M in Britton Robinson buffer solution at pH 7.0 and 4.00×10-7 to 1.00×10-4 M in serum samples. The precision of the method was detected by intraday and inter-day repeatability studies in the supporting electrolyte and serum samples media. CONCLUSION: The analytical applicability of the proposed method exhibited satisfying determination results for guaifenesin from pharmaceutical dosage forms (syrup) and human serum samples without any pre-separation procedures.

A new molecularly imprinted polymer for selective extraction and pre-concentration of guaifenesin in different samples: Adsorption studies and kinetic modeling.

This paper describes the synthesis of a molecularly imprinted polymer by chemical oxidation of pyrrole as the functional monomer, and at the presence of guaifenesin as the template. The prepared polymer was used as adsorbent in molecularly imprinted solid-phase extraction followed by spectrophotometric determination. Different parameters in the solid-phase extraction including sample pH, adsorbent weight, washing solution, and elution solvent were studied to determine optimum conditions for isolation and enrichment of guaifenesin. The results showed guaifenesin was quantitatively adsorbed on the molecularly imprinted polymer at pH 6.0 and completely eluted with an ethanol-water solution (50% v/v). An enrichment factor of four with satisfactory recoveries (87.0-95.0%) was obtained. The solid-phase extraction columns could be used for up to six consecutive elution-loading cycles without significant decreases in the analyte recoveries. The method had a dynamic range of 3.0 × 10-6 -1.5 × 10-4  mol/L with a limit of detection and limit of quantification of 1.4×10-6 and 4.5×10-6  mol/L, respectively. The proposed procedure was used for the extraction and determination of guaifenesin in different pharmaceutical formulations, with satisfying results being achieved.

In Situ Atmospheric Pressure Photoionization Mass Spectrometric Monitoring of Initial Pyrolysis Products of Biomass in Real Time.

Knowledge on the initial and intermediate pyrolysis products of biomass is essential for the mechanistic investigation of biomass pyrolysis and further optimization of upgrading processes. The conventional method can only detect the final products, which do not resemble the initial or intermediate pyrolysis products. Here, we introduce a direct orifice sampling combined with atmospheric pressure photoionization mass spectrometry (APPI-MS) for in situ online analysis of the evolved volatile initial products from the pyrolysis of biomass. Pyrolysis experiments of both dimeric model compound (guaiacylglycerol-ß-guaiacyl ether, GGGE) and poplar wood were carried out to validate the generality of the method. Generally, secondary reactions can be reduced by shortening the distance between the sample and sampling orifice. Large molecular-weight initial products up to trimers were detected during the pyrolysis of poplar wood, and no initial products larger than trimers were detected. It is inferred that in situ APPI immediately after sample extraction ensures efficient and effective product detection. Furthermore, the present work offers a promising feasible method for online tracing of reaction intermediates not only in pyrolysis but also in various reactive processes (e.g., catalytic reaction, oxidation) under operando conditions.

Robust Chromatographic Methods for the Analysis of Two Quaternary Mixtures Containing Paracetamol, Codeine, Guaifenesin and Pseudoephedrine or Phenylephrine in their Dosage Forms.

Two simple validated and highly selective methods for analysis of paracetamol, codeine, guaifenesin and pseudoephedrine or phenylephrine quaternary mixtures were developed. The first method is a high performance liquid chromatography with diode array detection method where separation was successful using Agilent C18 (150 × 4.6 mm) column, gradient elution of phosphate buffer pH 3, methanol and acetonitrile and diode-array detection at 210 nm. The second method is a HPTLC method followed by densitometric measurement of the spots at 257 nm. Separation was carried out on Merck HPTLC aluminum sheets of silica gel using methylene chloride: methanol: glacial acetic acid: ammonia (17.8: 1.68: 0.4: 0.12, v/v) mobile phase. The methods were applied successfully for analysis of both quaternary mixtures in laboratory-prepared tablets and also validated in regards to linearity, precision, accuracy, sensitivity and stability.

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.

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.

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

OBJECTIVE: 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). METHOD: 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. RESULT: 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%. CONCLUSION: 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.

Experimental Design Approach to Optimize HPLC Separation of Active Ingredients, Preservatives, and Colorants in Syrup Formulation.

Background: Preservatives and colorants in pharmaceutical products may be highly toxic, especially for sensitive individuals, when they are used in excessive amounts. In this context, sensitive and non-labor-intensive analytical methods with short analysis time for simultaneous quantification of these additive substances in drugs can meet all requirements in quality control laboratories. Objective: The aim of the study was to develop a simultaneous HPLC method for the analysis of pseudoephedrine HCl and guaifenesin, along with preservatives, methyl paraben and propyl paraben, and colorants, ponceau 4R and sunset yellow, in a syrup sample. Methods: Optimum conditions of HPLC separation were determined by Box-Behnken experimental design. Four independent variables of the separation were pH (6.0, 6.5, and 7.0) and flow rate of the mobile phase (2.0, 2.2, and 2.4 mL/min) and mobile phase ratios for the first and second gradient elutions (75, 80, and 85% for Gradient 1 and 50, 55, and 60% for Gradient 2 in terms of phosphate buffer percent, respectively). Results: The optimum conditions were found to be pH, 6.3; flow rate, 2.4 mL/min; and mobile phase ratios (phosphate buffer-acetonitrile) for Gradient 1 and 2, 85+15 (v/v) and 60+40 (v/v), respectively. Conclusions: Simultaneous analysis of all compounds was achieved by using this HPLC method with a short run time below 10 min. Highlights: This simple, rapid, and validated method is convenient and applicable for routine analysis of pharmaceutical products having similar composition without the need for any extraction step.

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.

Eco-Friendly Pharmaceutical Analysis of Multicomponent Drugs Coformulated in Different Dosage Forms Using Multivariate Curve Resolution and Partial Least Squares: A Comparative Study.

Background: Considering the environmental impact of analytical procedures necessitates replacing the polluting analytical methods with green alternatives. Objective: This study aims to develop and validate a multivariate curve resolution-alternating least-squares (MCR-ALS) method with correlation constraint for the simultaneous determination of theophylline, ambroxol, and guaifenesin as target analytes in the presence of methylparaben and propylparaben as interfering components. In addition, a partial least-squares regression (PLSR) method was also developed and optimized. Method: The developed methods were validated according to International Conference on Harmonization guidelines and successfully applied for the quantification of the target analytes in different pharmaceutical dosage forms. Results: Figures of merit such as root mean square error of prediction, bias, standard error of prediction, and relative error of prediction for both models were calculated, and they showed similar and satisfactory results. Correlation coefficients ranged between 0.9988 and 0.9992, reflecting high predictive ability. The optimized methods were compared with a reported HPLC method using one-way analysis of variance and showed no significant difference regarding accuracy and precision. Conclusions: The proposed chemometrics methods can be used as an eco-friendly alternative for chromatographic techniques for the quality control analysis of the studied mixture in different pharmaceutical dosage forms. Highlights: An MCR-ALS model was developed. The developed model was compared with a PLSR model. Both models were validated and successfully used for the determination of a multicomponent pharmaceutical mixture. The developed method is eco-friendly, fast, reliable, and cost-effective.

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.

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.

Development and validation of a generic high-performance liquid chromatography for the simultaneous separation and determination of six cough ingredients: Robustness study on core-shell particles.

A generally applicable high-performance liquid chromatographic method for the qualitative and quantitative determination of pharmaceutical preparations containing phenylephrine hydrochloride, paracetamol, ephedrine hydrochloride, guaifenesin, doxylamine succinate, and dextromethorphan hydrobromide is developed. Optimization of chromatographic conditions was performed for the gradient elution using different buffer pH values, flow rates and two C18 stationary phases. The method was developed using a Kinetex® C18 column as a core-shell stationary phase with a gradient profile using buffer pH 5.0 and acetonitrile at 2.0 mL/min flow rate. Detection was carried out at 220 nm and linear calibrations were obtained for all components within the studied ranges. The method was fully validated in agreement with ICH guidelines. The proposed method is specific, accurate and precise (RSD% < 3%). Limits of detection are lower than 2.0 µg/mL. Qualitative and quantitative responses were evaluated using experimental design to assist the method robustness. The method was proved to be highly robust against 10% change in buffer pH and flow rate (RSD% < 10%), however, the flow rate may significantly influence the quantitative responses of phenylephrine, paracetamol, and doxylamine (RSD% > 10%). Satisfactory results were obtained for commercial combinations analyses. Statistical comparison between the proposed chromatographic and official methods revealed no significant difference.

Green approach using monolithic column for simultaneous determination of coformulated drugs.

Green chemistry and sustainability is now entirely encompassed across the majority of pharmaceutical companies and research labs. Researchers' attention is careworn toward implementing the green analytical chemistry principles for more eco-friendly analytical methodologies. Solvents play a dominant role in determining the greenness of the analytical procedure. Using safer solvents, the greenness profile of the methodology could be increased remarkably. In this context, a green chromatographic method has been developed and validated for the simultaneous determination of phenylephrine, paracetamol, and guaifenesin in their ternary pharmaceutical mixture. The chromatographic separation was carried out using monolithic column and green solvents as mobile phase. The use of monolithic column allows efficient separation protocols at higher flow rates, which results in short time of analysis. Two-factor three-level experimental design was used to optimize the chromatographic conditions. The greenness profile of the proposed methodology was assessed using eco-scale as a green metrics and was found to be an excellent green method with regard to the usage and production of hazardous chemicals and solvents, energy consumption, and amount of produced waste. The proposed method improved the environmental impact without compromising the analytical performance criteria and could be used as a safer alternate for the routine analysis of the studied drugs.

Chemometrics resolution and quantification power evaluation: Application on pharmaceutical quaternary mixture of Paracetamol, Guaifenesin, Phenylephrine and p-aminophenol.

Three advanced chemmometric-assisted spectrophotometric methods namely; Concentration Residuals Augmented Classical Least Squares (CRACLS), Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) and Principal Component Analysis-Artificial Neural Networks (PCA-ANN) were developed, validated and benchmarked to PLS calibration; to resolve the severely overlapped spectra and simultaneously determine; Paracetamol (PAR), Guaifenesin (GUA) and Phenylephrine (PHE) in their ternary mixture and in presence of p-aminophenol (AP) the main degradation product and synthesis impurity of Paracetamol. The analytical performance of the proposed methods was described by percentage recoveries, root mean square error of calibration and standard error of prediction. The four multivariate calibration methods could be directly used without any preliminary separation step and successfully applied for pharmaceutical formulation analysis, showing no excipients' interference.

Determining the suitability of mass spectrometry for understanding the dissolution processes involved with pharmaceutical tablets.

RATIONALE: A current challenge for analytical chemists is the development of the measurement systems and approaches required to understand dynamic processes such as tablet dissolution. The design and development of oral tablets could be improved by the availability of detailed information about the rates of release of the individual tablet components. Small footprint mass spectrometry (MS) systems are gaining use for on-line reaction monitoring because of their ability to rapidly determine multiple reactant, intermediate, and product species. We have therefore assessed the utility of such MS systems to the study of dissolution processes. METHODS: Aqueous dissolution media containing phosphate and other non-volatile buffer salts were pumped from a standard USPII dissolution vessel through an active splitter and back. The splitter sampled the dissolution stream and diluted it into a make-up flow which was pumped to a small single quadrupole mass spectrometer. Single ion monitoring was used to quantify the ions of interest. Three different bio-relevant dissolution media were studied to gauge the effect of the sample matrix. RESULTS: Individual dissolution profiles were obtained from a tablet containing three drugs, and lactose as the soluble filler. This was successfully demonstrated with three different bio-relevant media designed to reflect the pH of the different sections of the human gastro-intestinal tract. Component concentrations as low as 0.06 µg/mL (representing 1% dissolution) were detected. The MS dissolution profiles correlated with the visual observation of tablet dissolution. MS gave linear responses with concentration for the individual components, although analysis of the tablet solution indicated that ion suppression is an area for further investigation. CONCLUSIONS: An on-line MS system was used to determine the individual dissolution profiles of three drugs and lactose as they were released from the same tablet. The level of each of these components in solution was determined every 10 seconds, and each had a similar release profile. The dissolution profiles were determined using inorganic buffer solutions at three different bio-relevant pHs.

Derivative emission spectrofluorimetry for the simultaneous determination of guaifenesin and phenylephrine hydrochloride in pharmaceutical tablets.

Rapid, simple and sensitive derivative emission spectrofluorimetric methods have been developed for the simultaneous analysis of binary mixtures of guaifenesin (GUA) and phenylephrine hydrochloride (PHE). The methods are based upon measurement of the native fluorescence intensity of the two drugs at λex = 275 nm in methanolic solutions, followed by differentiation using first (D1) and second (D2) derivative techniques. The derivative fluorescence intensity-concentration plots were rectilinear over a range of 0.1-2 µg/mL for both GUA and PHE. The limits of detection were 0.027 (D1, GUA), 0.025 (D2, GUA), 0.031 (D1, PHE) and 0.033 (D2, PHE) µg/mL and limits of quantitation were 0.089 (D1, GUA), 0.083 (D2, GUA), 0.095 (D1, PHE) and 0.097 (D2, PHE) µg/mL. The proposed derivative emission spectrofluorimetric methods (D1 and D2) were successfully applied for the determination of the two compounds in binary mixtures and tablets with high precision and accuracy. The proposed methods were fully validated as per ICH guidelines.