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Development and validation of RP-HPLC and HPTLC method of analysis for simultaneous estimation of ambroxol HCL, Dextromethorphan HBR and Guaifenesin in pharmaceutical cough cold preparation and statistical comparison of developed methods
Abstract
Pharmaceutical Cough Cold Preparations like syrup are widely used worldwide and mostly in countries like India. Aim and Objective of the study is to develop simple, precise, accurate, rapid and sensitive Method of Reverse Phase High Performance Liquid Chromatography (RP-HPLC) and High Performance Thin Layer Chromatography (HPTLC) for simultaneous estimation of Ambroxol HCl (AMB), Dextromethorphan HBr (DEX) and Guaifenesin (GUA) in Pharmaceutical Cough Cold Preparation and statistical comparison of both method was done. For RP-HPLC method Hibar RP-C18 (250mm × 4.6mm i.d. with particle size of 5μm) analytical column was used. The mobile phase composition used for RP-HPLC method was Acetonitrile - Methanol - 10mM Phosphate Buffer - 0.3% Triethyl Amine (25:15:60 v/v) and pH was adjusted to 3 using Orthophosphoric Acid. Flowrate was kept 1 mL/min. Detection was done at 205 nm using PDA detector. Linearity range for RP-HPLC method was found to be 3-10.5 μg/ml, 2-7 μg/ml and 10-35 μg/ml for AMB, DEX and GUA respectively. In HPTLC method Merck HPTLC plates precoated with 60F254 silica gel on aluminium plates were used as stationary phase. Mobile phase used in HPTLC method was Toluene - Methanol - Chloroform - Glacial Acetic Acid (6.5:1.5:1.5:0.5 v/v/v/v). Detection was done using Camag TLC scanner at 275 nm. Linearity range was found to be 1.5-3 μg/band, 1-2 μg/band and 5-10 μg/band for AMB, DEX and GUA respectively for HPTLC method. Statistical comparison of RP-HPLC and HPTLC was done by application of t-Test to recovery data of both methods. Finally concluded that A novel RP-HPLC and HPTLC methods were developed for simultaneous estimation of AMB, DEX and GUA in syrup dosage form. Both the method gives the good resolution for all three drugs. The developed method was validated and found to be sensitive, accurate, specific and reliable for simultaneous estimation of AMB, DEX and GUA in syrup dosage form. The proposed method can be used effectively in routine analysis.
... Literature review revealed that GUI and SAL were determined together by different analytical ISSN Print: 2229-7928 ISSN Online: 2230-7532 methods, such as (RP-HPLC) 7-10 , high-performance thin-layer chromatography (HPTLC) 11 , spectrophotometric 12 , spectroflourimetric 13 and chemometric 9 methods, while GUI and DEX were determined by RP-HPLC [14][15][16][17][18][19] , ultra highperformance liquid chromatography (UPLC) 20 , HPTLC 19 and chemometric 18 methods. Additionally, GUI and GUA were determined by HPLC 21 . ...
... Literature review revealed that GUI and SAL were determined together by different analytical ISSN Print: 2229-7928 ISSN Online: 2230-7532 methods, such as (RP-HPLC) 7-10 , high-performance thin-layer chromatography (HPTLC) 11 , spectrophotometric 12 , spectroflourimetric 13 and chemometric 9 methods, while GUI and DEX were determined by RP-HPLC [14][15][16][17][18][19] , ultra highperformance liquid chromatography (UPLC) 20 , HPTLC 19 and chemometric 18 methods. Additionally, GUI and GUA were determined by HPLC 21 . ...
... HPTLC chromatogram of a mixture of SAL (R f = 0.19) , GUI (R f = 0.48) and GUA (R f = 0.80) using ethyl acetate :hexane: methanol : ammonia ( 65: 35 :15 :2, by volume) as a developing system and scanning at 227nm. ...
Simple, selective and sensitive high-performance thin layer chromatographic (HPTLC) method has been developed and validated for the simultaneous determination of Guaifenesin (GUI) and its impurity Guaiacol (GUA), in two ternary mixtures with Salbutamol Sulfate (SAL) or Dextromethorphan HBr (DEX). The separation was carried out on HPTLC silica gel 60 F254 using ethylacetate: hexane: methanol: ammonia (65:35:15:2, by volume) as a developing system followed by densitometric measurement of bands at 227 nm for the first mixture containing GUI, SAL, GUA and by using ethylacetate: hexane: methanol: ammonia (65:35:5:2, by volume) followed by densitometric measurement at 275 nm for the second mixture containing GUI, DEX, GUA. Calibration curves were constructed in the range of (0.2–4 μg/band), (0.2–2 μg/band) and (0.4–1.2 μg/band) with good correlation for GUI, SAL and GUA, respectively, for the first mixture and in the range of (0.4–2 μg/band), (0.2–2 μg/band) and (0.4–1.2 μg/band) with good correlation for GUI, DEX and GUA, respectively, for the second mixture. The developed method was validated according to ICH guidelines and demonstrated good accuracy and precision. The results were statistically compared to the reported methods with no significant difference, indicating the ability of our method to be used for routine analysis of drug product.
... 16 Detection and quantification of active components in OTC preparations using thin layer chromatography and high performance thin layer chromatography has been reported. [17][18][19] Sagathiya et al. 20 used reverse phase high performance liquid chromatography and high performance thin layer chromatographic methods for the determination of dextromethorphan hydrobromide and guaifenesin in pharmaceutical cough-cold preparation. Darwish et al. ...
... Dragendorff's reagent was used to observe the separated components. Sagathiya et al. 20 found toluene:methanol:chloroform:glacial acetic acid (65:1.5:1.5:0.5 v/v/v/v) as the best solvent for the separation of ambroxol hydrochloride, dextromethorphan hydrobromide and guaifenesin in pharmaceutical preparations. Roy et al. 19 found methanol:ethyl acetate:concentrated ammonium hydroxide (2:17:1 v/v/v) as an appropriate solvent system for the separation of marketed paracetamol tablet. ...
In the present study, potential utility of thin layer chromatography to differentiate some common OTC cough–cold preparations was evaluated. Twenty solvent systems were examined from which a solvent systems A comprising methanol:ammonia in the ratio of 100:1.5(v/v) and B comprising chloroform:methanol in the ratio of 90:10(v/v) were found to be most suitable as it showed a high degree of separation of different components of these preparations. It was also found that iodine fuming technique is the best visualizing method for examining the TLC chromatograms of these drug samples prior to subsequent instrumental analysis.
... The correlation coefficient values for Salbutamol sulphate and Ambroxol hydrochloride were found to be respectively. [12][13][14][15][16][17][18][19][20] ...
Pharmaceutical analysis is imported branch of science deals with to check the identity, strength, quality and purity of chemical and herbal compounds. Qualitative analysis of drugs and pharmaceutical compounds. Quantitative analysis is of much importance and done by various methods. One of the most accurate and precise methods is spectrophotometry which comprises the measurement of intensity of electromagnetic radiation emitted or absorbed by the compound. Another most popular method of for quantitative analysis is high performance liquid chromatography (HPLC). In the present article a RP-HPLC method was developed for the simultaneous determination of salbutamol sulphate and ambroxol hydrochloride in oral liquid doses form and validation of the developed method. Developed methods include selection of mobile phase, chromatographic method, and wavelength whereas validation involves the system suitability, accuracy, precision, linearity, reproducibility, robustness, specificity and solution stability of the developed method. The result showed that the developed method is the best suited to the simultaneous determination of salbutamol sulphate and ambroxol hydrochloride and validated as per the standards.
... It may be acute due to different respiratory tract infections including common cold and flu, or chronic due to smoking and asthma. Cough is generally treated with some drug combinations [4]. Levocloperastine fendizoate, dextromethorphan hydrobromide and dexamethasone alone or in combination with antihistamines as chlorphenamine maleate are effective components used for treatment of cough resulting from common colds and allergy. ...
Sustainable chemistry established one of kind standards to maintain protection of environment through using safer mobile phase composition and/or lower solvent consumption. A fast green micellar HPLC method was developed and applied for the first time aiming at simultaneous determination of chlorpheniramine maleate, one of the most widely used antihistamine in combination with levochlopersatine fenodizoate or dextromethorphan hydrobromide or dexamethasone, in their pure forms, laboratory prepared mixtures and pharmaceutical dosage forms used in alleviating the symptoms of cough resulting from common colds and allergy. The separation was achieved on Kinetex C 18 column (100 mm × 4.6 mm i.d., 2.6-μm particle size) using micellar aqueous mobile phase consisting of (30 mM sodium dodecyl sulfate and 50 mM sodium dihydrogen phosphate, pH 5) and ethanol (85:15) with UV detection at 230 nm. The four drugs were successfully separated using isocratic elution in a single run not exceeding 7 min. According to ICH guidelines, the method was confirmed to be linear, accurate and precise over the concentration ranges of 5–60 μg mL ⁻¹ for chlorpheniramine maleate, 10–100 μg mL ⁻¹ for levocloperastine fenodizoate and dextromethorphan hydrobromide and 5–30 μg mL ⁻¹ for dexamethasone. In addition, the greenness of the developed method was assessed using two different tools indicating their least hazardous effect on the environment.
... In mixtures with other drugs, DXT has been determined in human plasma using HPLC-ESI-MS/MS [4] and HPLC with hollow fiber liquid phase microextraction [5] while in human plasma and urine, it was analyzed using excitation-emission matrix flu- orescence coupled with second-order calibration methods [6]. In pharmaceutical preparations, DXT in different drug mixtures has been analyzed using Ultra-Performance Liquid Chromatography (UPLC) [7], HPLC [8][9][10][11][12][13], HPTLC [14] and spectrophotometry [15][16][17]. ...
Two chromatographic methods were developed for the assay of the FDA approved lozenges containing dextromethorphan hydrobromide (DXT) and menthol (MNT). The first was a green HPTLC method which uses a mobile phase of methanol-ammonia (10:0.1, v/v). The densitometric measurements of the spots which were retained at 0.28 ± 0.01 for DXT and 0.76 ± 0.02 for MNT was done at 210 nm. The other method was RP-HPLC method with stability indicating merits at which a mixture of 20 mM phosphate buffer pH 3 and acetonitrile as mobile phase in isocratic mode was used. The cited drugs were resolved in RP-HPLC method using isocratic elution using 20 mM phosphate buffer: acetonitrile (65:35 v/v) with retention times of 2.21 and 3.47 min for MNT and DXT, respectively and quantified using 215 nm. Both methods were entirely validated and both methods were successfully able to analyze both drugs in presence of lozenges inactive ingredients. HPLC method had the advantage of being stability indicating at which resolution of the drugs from their forced degradation products was successfully attained. For HPTLC method, both drugs showed reasonable RF values when compared to rapidly eluted MNT in RP-HPLC; also it was more environmentally friendly than RP-HPLC as it used solvents which are less toxic and greener.
... Several HPLC methods were reported for simultaneous determination of Guaifenesin and other expectorants in pharmaceutical preparations (Gudipati et al 1991;Demian, 1993;Suzen et al 1999;Shuhan et al 2005;Suma et al 2013;Sagathiya and Bagada, 2014). The LC-MS method was also reported for quantification of Guaifenesin in human plasma (Andrew et al 2011). ...
... Aboul-Enein et al have successfully developed a method for the separation of GUA enantiomers in pharmaceutical application with Ambroxol HCl (AMB). 25 This method was superior over other reported LC [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] for determination of GUA enantiomers ( Figure 1A) along with AMB ( Figure 1B). ...
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 × 4.6 mm) as a chiral stationary phase and ethanol/water as a mobile phase with linear gradient elution of 20% to 70% ethanol in 6 minutes at a flow rate of 1.0 mL min−1 and UV detection at 270 nm. Linearity ranges were found to be 50 to 1000 μg mL−1 and 15 to 450 μg mL−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.
... For this reason, several researchers have worked at developing methods to simultaneously identify and quantify some or all the active ingredients in various formulations. Different protocols have been reported using various analytical facilities, including high-performance liquid chromatography (Çaglar & Büyüktuncel, 2014;Sagathiya & Bagada, 2014;Walode, Deshpande, & Deshpande, 2013;Kamatham, Kolli, Joga, Kumari, & Bharathi, 2013;Raghava et al., 2013;Korany, Fahmy, Mahgoub, & Hadir, 2011;Heydari, 2008;Palabiyik & Onur, 2007;Ali, Ghori, Rafiuddin, & Khatri, 2007;Golubitskii, Budko, Basova, Ivanov, & Kostarnoi, 2007;Sun, Lui, & Wang, 2006;El-Gindy, Mesbah, & Ghada, 2006;Grosa, Grosso, Russo, & Allegrone, 2006;El-Gindy, Emara, & Mostafa, 2006;Ozdemir, Aksoy, Dinc, Dumitru, & Saadet, 2006;Qi, Wang, Zhou, & Yan, 2003;Sawyer & Kumar, 2003;Burge & Raches, 2003;Paciolla, Jansen, Martellucci, & Osei, 2001;Ramos-Martos, Aguirre-Gomez, Molina-Diaz, & Capitán-Vallvey, 2001), ultra-performance liquid chromatography (Suneetha, Venkateswarlu, & Prasad, 2012), thin-layer chromatography (Abdelkawy, Metwaly, El Raghy, Hegazy1, & Fayek, 2011), UV spectrophotometry (Bankar, Lokhande, Sawant, & Ankita, 2013;Dinc, Baleanu, & Onur, 2002;Sena, Poppi, & N-way, 2004), high-performance thin layer chromatography (Ezhava, Bhalara, Rathod, & Dolarrai, 2014), electrophoresis (Dong, Chen, Chen, Chen, & Hu, 2005) and gas chromatography (Harsono, Yuwono, & Indrayanto, 2005). ...
... Another LC method has been reported for the determination of pseudoephidrine hydrochloride, GFN and Dexchlorpheniramine maleate in cough and cold medicines by using an ion pair-HPLC [6]. Sagathiya and Bagada have developed RP-HPLC and HPTLC methods for the simultaneous estimation of AML, Dextromethomorphen HBr and GFN in pharmaceutical cough cold preparation and statistical comparison studied by using RP-HPLC and HPTLC [7]. They employed a complicated mobile phase for the elution of the selected compounds. ...
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.
... Chemically, guaifenesin (GUA) [12,13] an antipruritic, anti-allergic, histamine H 1 antagonist (Fig. 2) is 3-(2-methoxyphenoxy) propan-1, 2-diol. Literature survey revealed that spectrophotometric [14][15][16][17], HPTLC [18], and HPLC [19][20][21][22][23][24] analytical methods have been reported for GUA individually or in combination with other drug/s. ...
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.
... In the literature about 6 methods were reported for the determining Ambroxol HCl alone, and in combination with other drug substancesin pharmaceutical formulation and in biological samples by using high performance thin layer chromatography (Kasture et al. 2010; Bagada et 2013).The HPTLC methods are shown in (Bhatia et al. 2008) Ambroxol HCl (AMB) and Guaifenesin (GUA) in presence of the oxidative degradate (AD) of AMB andguaicol (GD), the impurity of GUA MultivariateSpectrophotometric principal component regression (PCR) ,Partial least squares (PLS) 246nm (AMB) 273 nm(GUA) Methanol ----------- (Abdelkawy et al. 2011) Trivedi et al. 2011) ...
Context: Ambroxol Hcl is an active metabolite of bromohexine. It is an expectoration improver and a mucolytic agent used in the treatment of bronchial asthma and chronic bronchitis.The available formulation of Ambroxol was authorized first in market since 1978. Objective:This article highlights on published analytical methods reported in the literature for the determination of Ambroxol Hcl in biological samples and pharmaceutical formulations. Material and Methods: Various techniques like electrochemical, spectrophotometry, high-performance liquid chromatography (HPLC), liquid chromatography–mass spectrometry (LC–MS), Gas chromatography, Ultra performance liquid chromatography (UPLC) and high-performance thin layer chromatography (HPTLC) were used for the qualitative and quantitative estimation of Ambroxol Hcl. Result and Discussion: Literature reveals that most widely used diluents are methanol and distilled water in HPLC methods, which prolonged the run times with greater tailing factor. For spectrometric determination, the presence of multiple entities and excipients includes complexity with multi-component dosage forms, which could produce significant challenge to the analytical chemist during the development of assay procedure. For such instances, chemo-metric methods can be preferred to routine spectrophotometric methods. Conclusion: Amongst various analytical techniques available for the quantification of single and multicomponent dosage form. HPLC methods are most extensively used for analysis of Ambroxol Hcl.
Background:
Previous studies of dextromethorphan hydrobromide basically worked on simultaneous research with other compounds. So, the development of a novel method using the isocratic elution mode is needed.
Objective:
For the detection of dextromethorphan hydrobromide (DXM) in diverse matrices, a straightforward, accurate, and sensitive reversed-phase HPLC technique using a Waters 2487 Dual λ Absorbance detector has been designed and validated.
Method:
In this experimental work, utilizing methanol/pH 3.0 potassium dihydrogen phosphate buffer (70:30, v/v) as the mobile phase, the separation was completed in 7 minutes on a C-18 HPLC column (4.6 cm length, 4.6 mm internal diameter; 5 μm particle size) utilizing an isocratic elution mode, flow rate of 1.0 mL/min, and UV-detection at 278 nm. Integration of the chromatography response was carried out using Empower 2.4 software
Results:
With an R2 of 0.9987, the current approach showed high linearity for DXM in the 10- 60 ppm range (retention time 4.281 ± 0.505 min). For DXM Hbr, the limits of detection (LOD & LOQ) were 10.633 μg/mL and 32.221μg/mL, respectively. Samples remained stable in the presence of the matrices without any apparent influence.
Conclusion:
The novel approach, which used a straightforward liquid/liquid extraction procedure with recovery ranging from 100 ± 10 % performed by two different analytes, was accurate. The precision within and between days was ≤ 2.0% (RSD). The technique was proven to be reliable and repeatable, and it can be utilized with pharmacological (active ingredients, syrups) and also for biological (blood) matrices which can be used in future research work for bioanalytical method development such as pharmacokinetics studies.
The proposed methods are simple, rapid, and accurate, used for the determination of Ambroxol Hydrochloride (AMB.HCl). There were two methods, the First method included chromotrope 2R, chromotrope 2B, arsenazo I, ASPANDS, and chromotrope 2C for the determination of AMB.HCl in its pure and pharmaceutical forms. The first method is based on the drug oxidation with Potassium permanganate in excess. The unreacted potassium permanganate was determined by measuring the absorbance of colored chromotropic acid azo dyes namely chromotrope 2R, chromotrope 2B, arsenazo I, SPADNS, and chromotrope 2C. The suitable ƛmax were 500, 510, 500, 510, and 520 nm, respectively. Under optimized conditions, Beer’s Law showed good correlation and obeyed in the concentration range 1.51-7.46, 0.82-4.97, 1.65-6.63, 0.82-6.63, and 1.73-8.29 µg mL-1 for chromotrope 2R, chromotrope 2B, arsenazo I , SPADNS, and chromotrope 2C. The apparent molar absorptivity, Sandell sensitivity, LOD, and LOQ were calculated. Pure and pharmaceutical forms containing AMB.HCl were analyzed and tested for the validity of the proposed methods. The Second method spectrophotometric titration is based on the determination of unreacted potassium permanganate using spectrophotometric titration against ferrous ammonium sulfate, where the end-point was detected spectrophotometrically using ferrion indicator at 510 nm, the Relative standard deviation where 0.23-2.04 with average recovery 100.35-103%.
Ambroxol (AMB) is a member of the expectorant class, widely used as a secreolytic agent in patients to break up secretions. AMB is rapidly and effectively distributed from blood to tissue. The lungs have the highest concentration of AMB; accumulation of AMB in human lung tissue was detected at concentrations 15- to 20-fold greater than those reported in the circulation. Because of its wide range of actions and therapeutic applications may be worth looking into, particularly for respiratory symptoms, antioxidant, anti-inflammatory, influenza, and rhinovirus infections. Though several analytical methodologies have been established and confirmed for the AMB analysis in matrices of pharmaceutical and biological origins, novel sustainable, and economical methods are still to be choice of protocol to increase its sensitivity, reliability, and repeatability. Therefore, the present review offers an overview of critical analytical aspects regarding the HPLC, LC-MS/MS, HPTLC, capillary electrophoresis, spectrophotometry, and electrochemical methods for quantifying AMB in pharmaceutical and biological samples. Furthermore, this review will thoroughly discuss the physicochemical properties, stability, extraction conditions, instrumentation, and operational parameters of the targeted analyte. As a result, for the first time, this review complies with vital background information and an up-to-date interpretation of research undertaken by anticipated methodologies examined and implemented for the pharmaceutical analysis AMB.
A simple, step by step, cost-effective, accurate, sensitive, and selective validated High Performance Thin Layer Chromatographic method for simultaneous determination of Terbutaline sulphate, Ambroxol hydrochloride, and Guaifenesin in syrup formulation has been developed and validated. HPTLC separation was achieved on Merck aluminum HPTLC plates precoated with silica gel 60 F254. The solvent system comprised of Chloroform: Methanol: Ethyl acetate: Acetic acid: Formic acid (7.0:1.4: 0.8:1.0:0.5 v/v). Densitometric detection wavelength at 200 nm was used in reflectance-absorbance mode. The retention factors were found to be 0.32±0.02, 0.55± 0.02, and 0.72±0.02, for Terbutaline sulphate, Ambroxol hydrochloride, and Guaifenesin respectively. Results were found to be linear over a range of 200 - 700ng band-1, 1000 - 7000ng band-1, and 400-1200ng band-1 for Terbutaline sulphate, Ambroxol hydrochloride, and Guaifenesin, respectively. The percent assay was found to be 98.47%, 98.47%, and 99.23%, for Terbutaline sulphate, Ambroxol hydrochloride, and Guaifenesin, respectively in marketed formulation. The developed densitometric method was validated by following the International Council on Harmonisation (ICH) guideline. The developed and validated chromatographic method can be applied for routine quality control of Terbutaline sulphate, Ambroxol hydrochloride, and Guaifenesin in the combined syrup dosage form used in study.
In this review article, we will introduce all reported methods that have been developed for determination of certain anti-tussive and anti-histaminic drugs such as salbutamol, ambroxol and fexofenadine in their pure form, combined form with other drugs, combined form with degradation products, and in biological samples. We also will shed the light on the most important combination of drugs that are used for treatment of asthma and related diseases.
Guaifenesin is an expectorant and it is use to treat cough and congestion caused by the common cold, bronchitis, and breathing illness. The drug is official in Indian Pharmacopoiea, British Pharmacopoeia, and United States Pharmacopoeias. This article reviews the different analytical methods available for detection of Guaifenesin alone and in combination from various pharmaceutical formulations. They are many analytical techniques have been reported for simultaneous estimation of Guaifenesin and its combined pharmaceutical dosage form but only fewer methods have been reported for estimation of Guaifenesin alone. Some of those techniques are UV spectrophotometry, high-performance liquid chromatography (HPLC), high-performance thin layer chromatography (HPTLC), liquid chromatography-mass spectrometry (LC-MS), gas chromatography (GC), and ultraperformance liquid chromatography (UPLC). Amongst, various analytical methods are available for the quantification of single and multicomponent dosage forms.
A simple, sensitive, accurate, precise and rapid stability indicating HPTLC method for simultaneous determination of ambroxol hydrochloride and Loratadine in pharmaceutical dosage form has been developed. The study was performed on TLC aluminum plates precoated with silica gel 60F254 using chloroform: methanol (9:1V/V) as the mobile phase. This system gives compact and dense spots for both ambroxol hydrochloride (Rf value of 0.36±0.003) and loratadine (Rf value of 0.68±0.002). Densitometric analysis of both drugs was carried out in the reflectance absorbance mode at 216 nm. The coefficient of correlation data for the calibration plots showed a good linear relationship with R² = 0.997 ± 1.1224 in the range of 600-3600 ng for ambroxol hydrochloride and R² = 0.998 ± 0.0935 in the range of 50-300 ng for loratadine. The method was validated according to ICH guidelines for specificity, precision, robustness and recovery. Stability study shows that the chromatograms of samples from its degradation products were well resolved with significant Rf value. © 2018 Indian Drug Manufacturers' Association. All Rights Reserved.
The present study was aimed to develop and validate a simple, rapid, accurate, precise, and sensitive HPTLC method using DoE approach for the simultaneous estimation of erdosteine, guaiphenesin and terbutaline sulphate in syrup formulations. HPTLC separation was performed on aluminium plates precoated with silica gel 60 F254 as the stationary phase, three different factors like methanol content, chamber saturation time and distance travelled were optimized using Box-Behnken Design Good separation was obtained with toluene:dichloromethane:methanol:glacial acetic acid (4:4:1.81:0.2; % V/V/ V/V) mobile phase. Quantification was achieved by densitometric analysis of erdosteine, guaiphenesin and terbutaline sulphate over the concentration range of 500-3000, 200-1200 and 25-150 ng/band, respectively, at 225 nm. The method was validated for precision, accuracy, robustness, specificity, limit of detection and limit of quantitation as per ICH guideline. The method was successfully applied for the quantitative determination of erdosteine, guaiphenesin and terbutaline sulphate in in-house dosage form, i.e. syrup.
Two simple, rapid and economic UV spectrophotometric methods, namely successive ratio derivative and double divisor ratio spectra methods, have been developed for the simultaneous estimation of ternary mixtures of erdosteine, guaiphenesin and terbutaline sulphate without preceding separation steps. Method I is based on successive derivative of ratio spectra in two steps, whereas method II is based on convolution of double divisor ratio spectra, obtained by dividing the absorption spectrum of the ternary mixture by a standard spectrum of two of the three compounds in the mixture. All the drugs exhibited good linearity over the reported concentration range with acceptable correlation coefficient. The methods were validated according to ICH guidelines for the evaluation of accuracy, precision, sensitivity. The obtained relative standard deviation i.e. less than 2%, demonstrated that the proposed methods were accurate and precise and can be employed for routine analysis in quality control laboratories, eliminating the need of prior separation of the pharmaceutical mixtures.
Dextromethorphan (DXM) and diphenhydramine (DPH) are two commonly used over-the-counter non-narcotic antitussive drugs. Recent reports reveal the widespread abuse of DXM and DPH due to their euphoric and alcohol-like effects. Due to their medicinal importance as well as the apparent increase in their use as abused drugs, it has become critical to determine them in samples of biological, clinical and pharmaceutical interest. The electrochemical techniques for drug analysis have gathered considerable attention due to their pronounced selectivity, sensitivity and simplicity. The given review presents a compilation of published voltammetric and potentiometric methods developed for determination of DXM and DPH. It critically highlights the analytical performances, revealing the recent trends and progress in the specified approach for their analysis. The review forms a basis for further progress in this field and development of improved electrochemical sensors to determine the drug.
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A stability indicating, isocratic, rapid, specific, and sensitive high performance liquid chromatographic (HPLC) method was developed and validated for determination of Solifenacin in bulk drug. The quantitative determination of SOLIFENACIN was performed on a Hypersil C 8 (250mm × 4.6 mm i.d., 5 μm) column with mobile phase consist of 10 mM potassium dihydrogen phosphate buffer with 0.1% v/v TEA in Milli-Q water (pH-3): Acetonitrile (60:40 %v/v) pumped at a flow rate of 1 mL min -1 at 25°C. The eluents were monitored at wavelength 210 nm using photo diode array (PDA) detector. The drug was subjected oxidation, hydrolysis and heat to apply stress conditions. The developed method was validated as per ICH guideline for the parameters such as specificity, linearity, precision, accuracy, limit of detection, limit of quantification and found to be satisfactorily. The drug was found to be hydrolyzed in acidic and alkaline conditions. We also found the degradation under oxidative stress condition. The developed method was able to separate all degradation product generated under forced degradation studies and drug peak was eluted at 7.82 min. The response was linear in the drug concentration range of 1-30 μg mL -1 (r 2=0.9991) with limit of detection and limit of quantification 0.019 μg mL -1 and 0.063 μg mL -1 respectively. The Relative Standard Deviation (RSD) values for intra- and inter-day precision studies were 0.50% and 0.62% respectively. Mean % recovery (mean ± SD) was found to be 100.51 ± 1.98.
A simple and precise liquid chromatography method for the simultaneous estimation of Salbutamol sulfate, Guaifenesin, and Ambroxol hydrochloride in combined tablet dosage form was developed and validated. The chromatographic separation of the drugs was achieved with a Princeton sphere C-8 25 cm × 4.6 mm (Rankem) analytical column using buffer and methanol (58:42 v/v) as the mobile phase. The buffer used in mobile phase contained 0.1 M potassium dihydrogen phosphate and its pH was adjusted to 4.5 with 10% ortho-phosphoric acid. The instrument was set at a flow rate of 1.0 mL min, column at ambient temperature, and the wavelength of UV-visible detector at 220 nm. The method showed excellent linearity over a range of 5–35 µg mL for all the drugs. The correlation coefficients for Salbutamol sulfate, Guaifenesin, and Ambroxol hydrochloride were noted to be 0.9998, 0.9998, and 0.9995, respectively, and the mean recovery values were found to be 99.53%, 100.28%, and 100.05%, respectively. The proposed method could be suitable for quantitative determination of these drugs in pharmaceutical preparations and also for quality control in bulk manufacturing. The intermediate precision data was subjected to statistical analysis (F-test and t-test at 95% confidence level).
Simple, new flourimetric method is developed for Lisinopril by the condensation with 1‐Naphthylamine to form the fluorescent complex which is
measurable in the linearity range of 3‐ 16 μg/ml in methanol. The developed method was validated according to ICH guidelines for parameters like
accuracy, precision, specificity, ruggedness, robustness and percentage recovery. The Relative Standard Deviation was 0.44; recovery was 99‐100%.
Tablet formulations were used as sample for estimation and the results were found to be well within the specified limit. The developed method can
be applied successfully in estimation of Lisinopril in routine in‐processes of manufacturing.
A simple, precise and accurate reversed-phase liquid chromatographic method has been developed for the simultaneous estimation of Terbutaline Sulphate, Guaiphenesin and Ambroxol Hydrochloride in formulations. The separations were achieved on a 5-micron Waters symmetry C18 column (250 × 4.6mm) using a mobile phase consisting of a mixture of water and acetonitrile containing sodium hexane suphonate (pH 3.0). The detection of the constituents was done using UV detector at 280nm for Terbutaline Sulphate and Guaiphenesin and 250 nm Ambroxol Hydrochloride. The retention times of Terbutaline sulphate, Guaiphenesin and Ambroxol hydrochloride were approximately 3.8,6.2 and 21 minutes, respectively. Recovery study values of 98 to 102%, relative standard deviation of less than 2% for the assay, and linearity coefficient of 0.9999 show that the method is precise, accurate, and linear in the concentration given.
A simple, accurate and precise dual wavelength spectrophotometric method was developed for simultaneous determination of Drotaverine hydrochloride and Aceclofenac in combined pharmaceutical dosage form. The principle for dual wavelength method is "the absorbance difference between two points on the mixture spectra is directly proportional to the concentration of the component of interest". The wavelengths selected for determination of Drotaverine hydrochloride were 271.5 nm and 280.0 nm, whereas, the wavelengths selected for determination of Aceclofenac were 301.5 nm and 311.0 nm. Methanol was taken as a solvent. Regression analysis of Beer's plots showed good correlation in concentration range of 8-32 μg/ml for Drotaverine hydrochloride and 10-40 μg/ml for Aceclofenac. Accuracy of method was found between 98.33-101.5%. The precision (intra-day, inter-day and repeatability) of method was found within limits. The proposed method was successfully applied to determination of these drugs in commercial tablets.
A simple, reversed-phase HPLC method has been developed for rapid, simultaneous quantification of phenylephrine hydrochloride, guaiphenesin, ambroxol hydrochloride, and salbutamol (as salbutamol sulphate) in a commercial cough-cold liquid formulation. The compounds were separated on a 250 mm x 4.6 mm C(8) column with a gradient prepared from pH 3.0 phosphate buffer and 1:1 methanol-acetonitrile as mobile phase at a flow rate of 1.0 mL min(-1). Elution of the analytes was achieved in less than 15 min. Detection was by UV absorbance at 273 nm for phenylephrine hydrochloride and guaiphenesin and 225 nm for ambroxol hydrochloride and salbutamol. Percentage recovery and RSD were, respectively, 100.09% and 0.22% for phenylephrine hydrochloride, 100.43% and 0.50% for guaiphenesin, 100.91% and 0.70% for ambroxol hydrochloride, and 100.54% and 0.55% for salbutamol. The components of the syrup formulation were quantified on the basis of the peak areas obtained from freshly prepared standard solutions. The method was validated in accordance with ICH guidelines.
A novel stability - indicating LC assay method was developed and validated for quantitative determination of Ranolazine Hydrochloride (RAN) in bulk drugs and in pharmaceutical dosage form in the presence of degradation products generated from forced degradation studies. An isocratic, reversed phase LC method was developed to separate the drug from the degradation products, using a HiQ Sil C-18 HS, (250mm×4.6mm, 5μm) with methanol-water, 99:1 (%, v/v) as a mobile phase. The detection was carried out at the wavelength of 273nm. RAN was subjected to stress conditions of hydrolysis (acid, base, neutral), oxidation, photolysis and thermal degradation. Degradation was observed for RAN in acid, base and in 30% H2O2 conditions. The drug was found to be stable in the other stress conditions attempted. The degradation products were well resolved from the main peak. The percentage recovery of RAN ranged from (99.97 to 100.11%) in pharmaceutical dosage form. The developed method was validated with respect to linearity, accuracy (recovery), precision, specificity and robustness. The forced studies prove the stability-indicating power of the method.
The RP-HPLC (reverse phase high performance liquid chromatography) method was developed and validated for simultaneous determination of Multi drug components i.e., Theophylline, Etofylline, Guaiphenesine and Ambroxol Hydrochloride in a liquid dosage form. Chromatographic separation of the four drugs was performed on a Hypersil Phenyl BDS (25cmX4.6mm, 5mm). The mobile phase constituted of triethylamine pH 3.0 buffer: methanol (85:15) v/v was delivered at the flow rate 1.5 mL/min. Detection was performed at 235 nm. The peak purity of Theophylline, Etofylline, Guaiphenesine and Ambroxol Hydrochloride were 0.99970, 0.99979, 0.99986 and 0.99949 respectively. Calibration curves were linear with correlation coefficient between 0.99995 to 0.99997 over a concentration range of 5 to 37 microg/mL for Theophylline, 19 to 140 microg/mL for Etofylline, 20 to 149 microg/mL for Guaiphenesine and 6 to 45 microg/mL for Ambroxol hydrochloride. The relative standard deviation (RSD) was found < 2.0%. The percentage recovery was found between the range of 98.6% and 100.5% at three different levels. Robustness and ruggedness were performed and result found within the RSD of 2%. All the parameters of validation were found in the acceptance range of ICH guideline.