Pages Menu
ISSN (Online): 0975-8232,
ISSN (Print): 2320-5148

International Journal Of
Pharmaceutical Sciences And Research

IJPSR is indexed with Embase

An International Journal published monthly
An Official Publication of Society of Pharmaceutical Sciences and Research

Categories Menu

A REVIEW OF ANALYTICAL METHODS FOR ESTIMATION OF LEVOCETIRIZINE AND MONTELUKAST SODIUM IN COMBINED PHARMACEUTICAL DOSAGE FORMS

HTML Full Text

A REVIEW OF ANALYTICAL METHODS FOR ESTIMATION OF LEVOCETIRIZINE AND MONTELUKAST SODIUM IN COMBINED PHARMACEUTICAL DOSAGE FORMS

D. Bhutia, N. R. Bhuyan, B. Shrestha and V. R. Baraily *

Department of Pharmaceutical Analysis, Himalayan Pharmacy Institute, Majhitar, East Sikkim, India.

ABSTRACT: Beginning from simple analytical methods to the recent development of advanced hyphenated techniques stages, various analytical methods have been designed for the multicomponent analysis of drugs. Simultaneous estimation of drugs in the combined dosage form is vital in the pharmaceutical analysis since it is cost-effective and time-saving. Levocetirizine, the R-enantiomer of Cetirizine, is a peripheral H1-receptor antagonist used as a non-sedative antihistamine in treating chronic idiopathic urticaria, angioedema, and allergic rhinitis. Montelukast Sodium is selective cysteinyl leukotriene I receptor inhibitor that acts as an anti-asthmatic agent in the bronchial tubes and lungs. The combination of Levocetirizine with Montelukast Sodium in the pharmaceutical formulation is frequently used in the treatment of Allergic rhinitis as it has been shown to have additional benefits to the patients in reducing the symptoms efficiently. This review article has compared and addressed a variety of analytical methods applied for estimating Levocetirizine and Montelukast Sodium in the combined dosage form. The methods include UV Spectrophotometry methods, High-Performance Liquid Chromatography (HPLC), Ultra Performance Liquid Chromatography (UPLC), and High-Performance Thin-layer Chromatography (HPTLC). This review article also gives us insight into the development of different analytical techniques for estimating Levocetirizine and Montelukast Sodium combined with other drugs available in the market. The present paper suggests a suitable method for analyzing this pharmaceutical compound and helps optimize various analytical methods for their determination.

Keywords: Levocetirizine, Montelukast Sodium, Allergic rhinitis, Spectrophotometry, Chromatography

INTRODUCTION: Allergic rhinitis, a chronic inflammatory disease, is an IgE-mediated hypersensitivity disease of nasal airways caused mainly by airborne allergens, such as dust, pollen, molds, or animal dander.

It is also known as hay fever and is characterized by nasal congestion, rhinorrhea, an itchy nose, and sore throat 1. In this present era, Allergic rhinitis has become a significant health concern globally and has affected about 10-20% of the population throughout the world 2.

Levocetirizine, the R-enantiomer of Cetirizine chemically known as 2-(2-{4-[(R)-(4-chlorophenyl) (phenyl)-methyl] piperazin-1-yl} ethoxy) acetic acid, is a peripheral H1-receptor antagonist used as a non-sedative antihistamine in the treatment of chronic idiopathic urticaria, angioedema and allergic rhinitis 3, 4. Levocetirizine Dihydrochloride, having the molecular formula C21H25ClN2O3. 2HCL is the salt form of Levocetirizine with a molecular weight of 461.8 g/mol. It is a water-soluble, white crystalline powder 5, 6. This drug is officially listed in IP-2007 7. Montelukast Sodium, Monosodium salt of 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl) ethenyl] phenyl]-3- [2-(1-hydroxy-1-methyl ethyl) phenyl] propyl] thio] methyl] cyclopropane acetic acid appears as white to pale yellowish crystalline powder, which is very soluble in alcohol, dimethyl sulfoxide, and freely water-soluble while practically insoluble in acetonitrile. The molecular formula and molecular weight of Montelukast Sodium are C35H35ClNNaO3S and 608.2 g/mol, respectively 3. It is officially listed in IP-2010 8, BP-2016 9, and USP-2016 10. It inhibits the selective cysteinyl leukotriene I receptor in the bronchial tubes and lungs and acts as an anti-asthmatic agent 11.

FIG. 1: CHEMICAL STRUCTURE OF LEVOCETIRIZINE                        

FIG. 2: CHEMICAL STRUCTURE OF MONTELUKAST   SODIUM

Levocetirizine with Montelukast Sodium in combined dosage form has been shown to have additional benefits to the patients in efficiently reducing the symptoms of allergic rhinitis 12. Nowadays, various drugs in combined dosage forms have been researched and developed drastically due to their enhanced activity. The standard analytical procedures designed for these drugs may not be officially included in the pharmacopeia.

Hence, with the increasing demand, the need for new procedures that allow the rapid analysis of combined drugs has also enhanced. The simultaneous estimation of combined drugs ensures that the formulation contains the exact amount of active pharmaceutical ingredients as mentioned on the label. A broad range of simple and advanced analytical methods exist for determining Levocetirizine and Montelukast Sodium simultaneously 1, 13. A literature survey revealed that this drug product is most routinely determined by both analytical methods, including spectrophotometric and chromatographic methods.

Methodology: This study was conducted using the standard method of data searching using google and yahoo search engines. The obtained data are of standard electronic sources and mostly Scopus, PubMed, Science Direct, listed articles were preferred. The references and information were checked and cross-referenced to rectify errors and present the best-quality data.

Analytical Methods: There are several stages of drug development and manufacturing where analytical method development and validation play a significant role 14. The main purpose of method development is to establish an analytical method suitable for measuring the concentration of an Active Pharmaceutical Ingredient in a specific compounded dosage form. The method development process includes a method validation process which serves to verify and assure the developed method by studying various validation parameters that include linearity, range, accuracy, precision, specificity, detection limit, quantitation limit, and robustness of the methods, thereby indicating the suitability of the developed method for determination of pharmaceutical compounds from bulk and pharmaceutical formulations 1, 15. Analytical methods developed for estimating Levocetirizine and Montelukast Sodium are as follows:

Spectrophotometric Method: Spectro-photometric methods for estimating Levocetirizine (LEV) and Montelukast Sodium (MKT) in bulk and combined pharmaceutical dosage forms were studied and have been summarized in Table 1.

TABLE 1: UV SPECTROPHOTOMETRY METHOD

Sl. no. Drug Combination Method Descriptions Ref.
1. Levocetirizine Hydrochloride and Montelukast Sodium in Tablet Dosage Form Absorbance correction method Solvent: Methanol Detection wavelength: 287nm (λ max of MKT) 232nm (λ max of LEV) Linearity range: 2-40 µg/mL (MKT at 287 nm, 232 nm) 1-40 µg/mL (LEV at 232 nm) r2 value: 0.9997 (MKT at 287 nm) 0.9999 (MKT at 232 nm) 0.9996 (LEV at 232 nm) % RSD (label claim):0.4422 % (MKT) 1.0826 % (LEV) % Recovery range:  99.70 % (MKT) 100.49 % (LEV)  

16
2. Levocetirizine Hydrochloride and Montelukast Sodium in Tablet Dosage Form Multi-

wavelength method

 Solvent: Methanol Detection wavelength: 229 nm, 232.2 nm, 232 nm Linearity range: 5-40µg/mL (MKT at 229 nm, 232.2nm) r2 value: 0.999921(MKT at 229 nm) 0.999795(MKT at 232.2 nm) % RSD (label claim): 1.3069 (MKT) 0.1802 (LEV) % Recovery range: 98.58 % (MKT) 100.49 % (LEV)  

16
3. Levocetirizine Hydrochloride and Montelukast Sodium in Tablet Dosage Form

 

 

 First-order derivative method Solvent: Methanol Detection wavelength: 231.1 nm (zero crossing point for LEV) 216.5nm (zero crossing point for MKT) Linearity range: 10-40µg/mL (MKT at 231.1nm)

10-40 µg/mL(LEVat 216.5 nm) r2 value: 0.99970 (MKT at 231.1 nm) % RSD (label claim): 1.71029 (MKT)

1.0215 (LEV) % Recovery range: 99.76 % (MKT) 99.82 % (LEV)

  

16
4. Montelukast Sodium and Levocetirizine Dihydrochloride in Tablet Dosage Form Ratio derivative spectrophotometricmethod Solvent: Methanol Detection wavelength: 250.4 nm (MKT) 238.4 nm (LEV) Linearity range: 4-12 µg/mL (MKT)

2-6 µg/mL (LEV) r2 value: 0.999, 0.997 (MKT, LEV)

% Purity:96.86 % (MKT), 99.63 % (LEV) % Recovery Range: 99.79% to 100.68% (MKT) 99.44 % to 100.2 % (LEV) %RSD (Precision): less than 2 % LOD: 0.09 µg/mL (MKT), 0.178 µg/mL (LEV) LOQ: 0.277µg/mL (MKT), 0.591µg/mL(LEV)

  

17
5. Montelukast Sodium and Levocetirizine Dihydrochloride

in Tablet Dosage Form

 AUC curve method Solvent: Methanol Detection wavelength: 263.6 nm-293.6 nm

222 nm-242nm Linearity range: 5-30 µg/mL for both API

r2value: 0.9969, 0.9988 for MKT at both wavelength range, 0.9991 for LEV at 222 nm-242nm % Purity: 98.90% for MKT 98.75 % for LEV %RSD (Precision): less than 2 % % Recovery: near to 100% LOD (µg/mL): 1.60 at 222 nm-242 nm (MKT) 1.06 at 263.6 nm-293.6 nm (MKT)

1.23 at 222 nm-242nm (LEV) LOQ (µg/mL): 4.80 at 222 nm-24nm (MKT) 3.1 at 263.6 nm-293.6 nm (MKT)

3.71at 222 nm-242nm (LEV)

  

18
6. Levocetirizine

Dihydrochloride and Montelukast sodium in

Tablet Dosage Form

 Ratio spectra

first derivative spectrophotometricmethod

 Solvent: Methanol Detection wavelength:240 nm (LEV)

281 nm (MKT) Linearity range: 2-32 µg/mL (LEV)

3-30 µg/mL (MKT) r2 value: 0.9995, 1.000 (LCT, MKT)

%RSD (Accuracy, Precision): less than 2 % % Purity: Montek-LC: 101.34% (LEV) 99.68 % (MKT) Montair-LC: 100.64% (LEV) 99.48% (MKT) % RSD (Robustness): less than 2 %                  LOD (µg/mL): 0.2979182, 0.3177621 (LEV, MKT) LOQ (µg/mL): 1.8263959, 2.4459207 (LEV, MKT)

  

19
7. Levocetirizine Dihydrochloride and Montelukast Sodium in

Tablet Dosage Form

 First-orderderivative spectrophotometricmethod Solvent: 0.5% w/v Sodium Lauryl Sulphate in distilled water Detection wavelength:  350.2 nm (zero crossing point for LEV) 211.8 nm (zero crossing point for MKT) Linearity range: 3-30µg/mL for both API r2 value: 0.9994 (MKT),0.9999 (LEV) % Purity: Telekast -L®- 98.6 % (MKT)

99.2 % (LEV) Bulk Drug- 101.84% (MKT)

100.88 % (LEV) % Recovery: 98.40 % to 100.50 % (MKT) 99.30 % to 101.25% (LEV) %RSD (Precision): less than 2

LOD: 0.993µg/mL (MKT), 0.361µg/mL (LEV) LOQ: 3.0 µg/mL (MKT), 1.09 µg/mL (LEV)

  

20
8. Montelukast Sodium and Levocetirizine Hydrochloride in a binary mixture

 

 Simultaneous equation method Solvent: Methanol Detection wavelength: 284 nm (λmax of MKT) 229 nm (λmax of LEV) Linearity range: 4-20 µg/mL (MKT) 2-10 µg/mL (LEV) r2 value: less than 1 for both drug

% Purity: 99.08 %-99.87 % (MKT) 98.5 %-101 % (LEV)

% Recovery: 98.5 %-101.1 % % RSD (Precision, Accuracy): less than 2 LOD: 1.1µg/mL(MKT), 3.3 µg/mL (LEV)

LOQ: 0.7µg/mL(MKT), 2.1 µg/mL(LEV)

  

21
9. Levocetirizine Dihydrochloride and Montelukast Sodium in Tablet Dosage Form Bivariate calibration algorithm

Method

 Solvent: Methanol Detection wavelength: 220 nm, 230 nm

Linearity range: 4–28µg mL-1 for both drugs r2 value: 0.9991 (LEV) 0.9992 (MKT) LOD (µg/mL): 0.261 (LEV) 0.079 (MKT) LOQ (µg/mL):0.893 (LEV) 0.264 (MKT) % RSD (Precision, Accuracy): less than 2 % Recovery:  99.41 % (LEV) 100.58 % (MKT)

  

22

 

 
10. Levocetirizine Dihydrochloride and Montelukast Sodium in Tablet Dosage Form

 

 Dual wavelength

Method

 Solvent: Methanol Detection wavelength: 208 nm, 214.4 nm (MKT) 355 nm, 390 nm (LEV)  Linearity range: 4–28 µgmL-1 for both drugs r2 value: 0.9990 (LEV at 208 nm, 214.4 nm) 0.9989 (MKT at 355nm, 390 nm) LOD (µg/mL): 0.374 (LEV)

0.273 (MKT) LOQ (µg/mL): 1.249 (LEV) 0.190 (MKT)

%RSD (Precision, Accuracy): less than 2 % Recovery: 99.11 % (LEV) 98.62 % (MKT)

  

22
11. Levocetirizine Dihydrochloride and Montelukast Sodium in Tablet Dosage Form

 

 Second derivative spectrophotometric method Solvent: Methanol Detection wavelength: 244 nm, 293.2 nm, 335.6 nm Linearity range: 4–28 µgmL-1 for both drugs

r2 value:0.9990(LEV at 244nm) 0.9986 (MKT at 293.2 nm, 335.6 nm) LOD (µg/mL): 1.177 (LEV at 244 nm) 0.785 (MKT at 293.2 nm) 0.884 (MKT at 335.6 nm) LOQ(µg/mL): 3.921 (LEVat 244nm) 2 .61 (MKT at 293.2nm) 2.818 (MKT at 335.6nm) %RSD (Precision, Accuracy): less than 2%

% Recovery:  99.16 % (LEV at 244 nm) 100.53 % (MKT at 293.2 nm) 102.00 % (MKT at 335.6 nm)

  

22
12. Levocetirizine Dihydrochloride and Montelukast Sodium in Tablet Dosage Form Ratio difference method Solvent: Methanol Detection wavelength: 216 nm, 232 nm (LEV) 296.4 nm, 344.2 nm (MKT) Linearity range: 4–28 µgmL-1 for both drugs r2 value: 0.9979 (LEVat 216 nm, 232 nm)  0.9986 (MKT at 296.4 nm, 344.2 nm) LOD(µg/mL): 0.229 (LEV) 0.352 (MKT) LOQ(µg/mL): 0.764 (LEV) 1.152 (MKT) %RSD (Precision, Accuracy): less than 2 % % Recovery: 100.5 % (LEV) 99.01 % (MKT)  

22
13. Montelukast Sodium and Levocetirizine Hydrochloride in

Tablet Dosage Form

 Simultaneous equation

Method

 Solvent: Methanol Detection wavelength: 267 nm (λmax of MKT) 225 nm (λmax of LEV) Linearity range:5-25 µg/mL(MKT) 2.5-12.5 µg/mL (LEV) r2value: 0.9991 % (MKT) 0.9994 % (LEV) % Purity:99.02% (MKT), 100.04% (LEV) %Recovery: 99 %-100%. %RSD (Precision, Accuracy): less than 2 % L0D (µg/mL): 0.2 (MKT), 0.6 (LEV) L0Q (µg/mL): 0.6 (MKT), 1.8 (LEV)  

11
14. Levocetirizine Dihydrochloride and Montelukast Sodium in

Tablet Dosage Form

 First-order derivative spectroscopy

method

 

 Solvent: 0.1N NaOH Detection wavelength: 291.60 nm (Zero crossing point of LEV) 238.20 nm (Zero crossing point of MKT) Linearity range: 5-30 µg/mL for LEV 10-60µg/mL for MKT r2 value: 0.9994 for LEV 0.9950 for MKT

% Purity: 99.4 % (LEV) 101.73 % (MKT) % RSD (Accuracy, Precision)): less than 2 LOD Value: 1.05µg/mL for LEV 3.69µg/mL for MKT LOQ Value: 3.21 µg/mL for LEV

11.17 µg/mL for MKT

  

23

To estimate Levocetirizine and Montelukast Sodium levels in combined pharmaceutical formulations, various spectrophotometric methods have been developed over the years. This paper describes the spectrophotometric methods that have been developed from the year 2009 to 2016. Multi-wavelength method, Absorbance correction method, Derivative spectrophotometric method, AUC curve method, Simultaneous equation method, Bivariate calibration algorithm method, Dual-wavelength method, Ratio difference method, and Absorbance Factor method are the developed methods that have been demonstrated for their estimation under different analytical conditions. After reviewing various spectrophotometric methods designed for estimating Montelukast Sodium and Levocetirizine in combined dosage form, it was revealed that methanol is the most used solvent. Wavelengths used were in the range of 200-400nm for their detection. The simultaneous equation method, also known as Vierordt’s method, is frequently used due to its simplicity and also consumes less time compared to other methods requiring tedious sample preparation. The derivative spectrometry method is the most extensively used method where co-formulated drugs come across the problem of interference due to spectral overlapping as derivative spectra show better resolution and help identify the compounds having close λ max to one another. The bivariate calibration algorithm method developed by Noha S. Rashed et al., 2015 proves to be the most sensitive method, having the lowest LOD values with a linearity range of 4-20 µg/ml for Montelukast Sodium and 2-10 µg/ml for Levocetirizine respectively 22. The ratio derivative spectroscopic method has the advantage of selecting suitable divisor concentration, making it dominant over other methods in terms of sensitivity and accuracy. All the developed spectrophotometric methods for estimating Levocetirizine and Montelukast Sodium were simple, precise, accurate, and reproducible.

Chromatography: Chromatographic methods for estimating Levocetirizine and Montelukast Sodium in bulk and combined pharmaceutical dosage forms were studied and summarized in Table 2.

TABLE 2:  CHROMATOGRAPHIC METHOD

Sl. no. Drug combination Method Analytical Conditions Ref.
1. Montelukast Sodium and Levocetirizine Dihydrochloridein

Tablet Dosage Form

 

 HPTLC Stationary phase: Silica gel 60F254 aluminum plate (20x 10 cm)

Mobile phase: Ethyl acetate: methanol: triethylamine (5:5:0.02 v/v/v)

Internal standard: Paracetamol Detection wavelength:240 nm

Run time: 7 min Rf value: 0.29, 0.50, 0.6 (LEV, MKT, PARA)

Linearity range:400–1200 ng/spot (MKT) 200–600 ng/spot (LEV)

r2value:0.9993 (MTK), 0.9985 (LEV) % RSD (Precision, Accuracy): less than 2 % % Recovery: 90% to 120.0% LOD: 20.63 ng/spot (MKT) 21.12 ng/spot (LEV) LOQ: 62.5 ng/spot (MKT)

64 ng/spot (LEV)

  

23
2. Levocetirizine

Dihydrochloride and Montelukast Sodium in Tablet Dosage Form

 

 RP-HPLC

 

 Column: SUPELCOSILTM, LC-8 column (15cm x 4.6mm)

Mobile phase: 0.02M Potassium dihydrogen phosphate buffer solution: methanol (40:60 v/v) Detection wavelength: 218nm

Flow rate: 1.0mL/min Run time: 10 min Retention time: 4.30 min (LEV), 7.408 min (MKT) Linearity range: 5-20 µg/mL (LEV) 10-40µg/mL (MKT) r2 value: 0.993 (LEV), 0.997 (MKT) % Purity: 99.18 % (LEV), 99.08 % (MKT) %RSD (Precision, Accuracy): less than 2 % LOD: 2.493µg/mL(LEV), 0.489µg/mL(MKT) LOQ: 7.553 µg/mL (LEV), 1.482µg/mL(MKT)

  

24
3. Levocetirizine Dihydrochloride

and Montelukast Sodium in Tablet Dosage Form

 RP-HPLC Column: BDS Hypersil C18column (250 mmx4.6mm) Mobile phase: Disodium hydrogen phosphate buffer (0.02M): Methanol (25:75 v/v)

Detection wavelength: 231 nm, Flow rate: 1.0 mL/min Retention time: 3.558 min, 7.450 min (LEV, MKT) Linearity range: 1 – 10 µg/ mL (LEV) 2 – 20 µg /mL (MKT) r2 value: 0.9987 (LEV), 0.9980 (MKT) LOD: 0.5 µg/mL (LEV), 0.2 µg/mL (MKT) LOQ: 0.8 µg/mL (LEV), 0.6 µg/mL (MKT) % RSD (Precision): less than 2%

% Purity:99.76 % (LEV) 100.15 % (MKT)

  

25
4. Levocetirizine Dihydrochloride

and Montelukast Sodium in Tablet Dosage Form

 RP-HPLC Column: Waters C18analytical column (15cm × 4.6 mm, 5µ) Mobile phase: Methanol: water (75:25 v/v) Detection wavelength: 235nm

Flow rate: 1.0 mL/min Run time: 7 min Retention time: 2.88 min, 3.83 min (LEV, MKT) Linearity range: 50-150 µg/mL (LEV)

100- 300 µg/mL (MKT) r2 value:0.9991, 0.9994 (LEV, MKT)

% Recovery: 100 % (LEV), 99 % (MKT) %RSD (Precision): less than 2 % LOD:0.42 ng/mL, 0.16 ng/mL (LEV, MKT)

LOQ: 0.36 ng/mL, 0.12 ng/mL (LEV, MKT)

  

26
5. Levocetirizine

and Montelukast Sodium in Tablet Dosage Form

 RP-HPLC Column: Atlantis C18 analytical column (4.6×150

mm, i.d.5µm) Mobile phase: Acetonitrile: ammonium acetate (65:35 % v/v), Detection Wavelength: 230nm Flow rate: 1.0 mL/min

Run time: 13 min Retention time: 3.03min, 6.28 min (LEV, MKT)

Linearity range:25-75 µg/mL (LEV) 50-150 µg/mL(MKT)

r2 value: 0.999 % Purity: 99.2%- 102.4 %  %RSD (Precision, Accuracy): less than 2 % LOD: 0.05 µg/mL, 0.10 µg/mL (LEV, MKT) LOQ: 0.17 µg/mL, 0.33 µg/mL(LEV, MKT)

  

27
6. Levocetirizine Dihydrochloride and Montelukast Sodium in

Tablet Dosage

Form

 RP-HPLC Column: Hypersil BDS C18column (250×4.6 mm, 5μm) Mobile phase: Phosphate buffer: acetonitrile (40:60% v/v) Detection wavelength: 230 nm Flow rate: 1.0 mL/min Run time: 10 min

Retention time:3.06 min,6.76 min (LEV, MKT) Linearity range:12.56–37.68 μg/mL (LEV) 23.78–71.20 μg/mL (MKT)

r2value: 0.9998  % Purity: 99.55 %(LEV), 98.37 % (MKT) %RSD (Precision, Accuracy): less than 2 % LOD: 0.079 µg/mL (LEV), 0.156 µg/mL (MKT) LOQ: 0.239 µg/mL (LEV), 0.473 µg/mL (MKT)

  

28
7. Levocetirizine Dihydrochloride and MontelukastSodium in Tablet Dosage Form

 

 HPTLC

 

 Stationary phase: Silica gel60 F254aluminum plate(20 × 10 cm)

Mobile phase: Toluene: ethyl acetate: methanol: ammonia (2.5: 7: 2.5: 1,v/v/v/v)  Detection wavelength: 231 nm Run time: 25 min Rf value: 0.31, 0.44 (LEV, MKT) Linearity range:500-2500 ng spot-1 (LEV) 1000-5000 ng spot-1 (MKT) r2 value: 0.9981 (LEV) 0.9982 (MKT)  % (Precision, Accuracy):  less than 2%

% Purity: 99.72 % (LEV) 100.19 % (MKT) LOD: 90 ng spot-1 (LEV), 50 ng spot-1 (MKT) LOQ: 200 ng spot-1 (LEV), 110 ng spot-1 (MKT)

  

25
8. Montelukast Sodium and Levocetirizine Hydrochloride in

Tablet Dosage Form

 HPTLC Stationary phase: Silica gel 60 F254 aluminum sheets (10 x 10 cm)

Mobile phase:n- Hexane: chloroform: methanol: acetic acid (3.5:5.0:1.2:0.3 v/v/v/v) Detection wavelength: 302 nm

Rf value: 0.29, 0.65 (MKT, LEV) Linearity range: 5-15 µg/mL (MKT) 2.5-7.5 µg/mL (LEV) r2 value:0.9993, 0.9998 (MKT, LEV)

% RSD (Precision): 0.28, 0.31(MKT, LEV) % Purity: 99.02% (MKT), 100.04% (LEV) LOD (ng/spot): 100, 110(MKT, LEV) LOQ (ng/spot): 210, 240 (MKT, LEV)

  

11
9. Montelukast Sodium and Levocetirizine Hydrochloride in

Tablet Dosage Form

 RP-HPLC Column: Inertsil ODS column (250 x 4.6 mm, 5µ) Mobile phase: Buffer: Methanol (35: 65 v/v) Detection wavelength: 234 nm

Flow rate: 1.5 mL/min Run time: 10 min Linearity range: 4-20 μg/mL (MKT) 2-10 μg/mL (LEV) r2 value: 0.999847 (MKT)

0.999824 (LEV)    %RSD (Precision): 0.5 (MKT), 0.3 (LEV)

% RSD (Accuracy): 0.4 (MKT), 0.3 (LEV) % Purity: 99.02% (MKT), 100.04% (LEV) LOD: 1.85µg/mL(MKT), 1.63 µg/mL(LEV) LOQ: 3.42 µg/mL(MKT), 4.14 µg/mL (LEV)

  

11
10. Levocetirizine Hydrochloride and MontelukastSodium in Tablet Dosage Form RP-HPLC Column: HypersilGold L7column (250mm x 4.6mm, 5µm)

Mobile phase:  0.05 M Potassium Dihydrogen Phosphate Buffer: Methanol (20:80 v/v) Flow rate: 1.2 mL/min Detection wavelength: 225 nm Retention time:3.2 min, 4.2 min (LEV, MKT) % Purity:99.2%, 100.3% (LEV, MKT) Linearity range (mcg/mL): 10-260 (LEV) 10-350 (MKT) r2 value: 0.9998, 0.9999(LEV, MKT)

LOD (mcg/mL): 2.26 (LEV) 2.41 (MKT) LOQ (mcg/mL): 6.85 (LEV) 7.3 (MKT)

  

29
11 Montelukast Sodium and Levocetirizine Dihydrochloride in Liquid Dosage Forms RP-UPLC

 

 Column: AQUITY BEH phenyl column (50mm x 2.1mm, 1.7µm)

Mobile phase: Potassium dihydrogen phosphate(2.72 gm) to 1 L of Milli Q water Diluent: Water: methanol (10:90 v/v) Flow Rate:0.4 mL/min Detector: PDA (photo diode array) detector Detection wavelength: 231 nm

Run time:3.5 min Retention Time:0.587 min, 1.626 min (LEV, MKT) r2 value: 0.999 for both API % RSD (Accuracy, Precision):  less than2.0 %

  

30
12 Levocetirizine

dihydrochloride and Montelukast sodium in Tablet Dosage Form

 RP HPLC Column: Phenomex-luna 5µ C8 (2) column (100Å, 250 X 4.6 mm)

Mobile phase: Acetonitrile: 0.5% triethylamine in water (90:10 v/v)

Flow rate: 0.8 mL/min Detection Wavelength: 231 nm  Retention time: 3.8 and 5.2 min (LEV and MKT) Linearity range (µg/mL): 2-32, 3-30(LEV, MKT) r2 value:0.9997, 0.9994(LEV, MKT) % Purity:

Montek-LC-99.18%,100.26% (LEV, MKT)  Montair LC-99.83%, 98.28% (LEV, MKT) % RSD (Accuracy, Precision):  below 2.0 % LOD (µg/mL): 0.00028, 0.0032(LEV, MKT) LOQ (µg/mL): 0.00086, 0.0094 (LEV, MKT)

  

19
13. Montelukast Sodium and Levocetirizine Dihydrochloride in Tablet Dosage Form HPTLC Stationary Phase: Silica gel 60 F254aluminum plate (10 x 10 cm)

Mobile phase: Chloroform: methanol: toluene: glacial acetic acid (10:5:3:0.5v/v/v/v) Detection wavelength: 269.0 nm, 302 nm

Linearity range: 400-4500 ng r2 value: 0.9998 Rf value: 0.89 and 0.64 (MKT and LEV) LOD (µg/mL): 1.536, 2.864 (MKT, LEV) LOQ (µg/mL): 2.536, 3.453 (MKT, LEV)

  

31
14. Levocetirizine Hydrochloride and Montelukast Sodium in Tablet Dosage Form HPTLC Stationary Phase: Silica gel aluminum plate 60 F254 (20 ×10 cm)

Mobile phase: Toluene: Ethyl Acetate: Methanol (2.5: 5: 2.5v/v/v) Detection wavelength: 240 nm Rf value: 0.17, 0.76 (MKT, LEV)

Linearity range:2-10µL for both API r2 value: less than0.99

% RSD (Precision):less than 2 % Purity: 99.14 % (LEV), 99.28 % (MKT) LOD (ng band-1): 44.43, 29.12 (MKT, LEV) LOQ (ng band-1):134.66, 88.24(MKT, LEV)

  

32
15. Montelukast and Levocetirizine in Liquid dosage Form RP-HPLC Column: Hypersilwaters C18 column (4.6mm × 250mm ×5µm)

Mobile phase: Phosphate buffer: acetonitrile (55:45) Flow rate: 1 mL/min  Detection wavelength: 228 nm Run time: 6 min  Retention time: 2.47 min, 2.823 min (MKT, LEV) Linearity range:40-20 µg/mL for MKT 25-75 µg/mLfor LEV r2 value: 0.999 % Recovery: 99.10 %, 99.38 % (MKT, LEV) % RSD (Accuracy, Precision): less than 2 % % Purity:98.65%,99% (MKT, LEV)

  

33
16 Montelukast and Levocetirizine in

LiquidDosage Form

 RP-HPLC Column: Hypersil BDS column(250 x 4.6 mm, 5µm)

Mobile phase: Potassium di-hydrogen phosphate buffer: Acetonitrile (35:65) Flow rate: 1mL/min Detection wavelength:231nm Retention time: 2.599min, 3.472min (MKT, LEV) Linearity range: 25-150µg/mL (MKT) 12.5-75 µg/mL (LEV) r2 value: 0.999 for both drugs % RSD: less than2 LOD: 0.04µg/mL,0.08 µg/mL (MKT, LEV) LOQ: 0.11 µg/mL,0.25µg/mL (MKT, LEV) % Recovery: 99.88%, 99.9%for (MKT, LEV)

  

34
17. Montelukast Sodium and Levocetirizine Hydrochloride in Tablet Dosage Form

 

 HPTLC Stationary phase: Silica gel 60F 254 aluminium sheets (20 x 10 cm)

Mobile phase: Chloroform: benzene: methanol: toluene (5:7.2:1:0.2 v/v/v/v) Detection wavelength: 286 nm Linearity range: 500-1500 ng spot-1 (MKT) 1000-5000 ng spot-1 (LEV) r2 value: 0.9992, 0.9995 (MKT, LEV) % RSD (Peak area value): 1.09, 1.17 (MKT, LEV)

% Purity: 100.40 % (MKT) 98.40 % (LEV) LOD: 170 ng/spot, 20 ng/spot (MKT, LEV) LOQ: 570 ng/spot, 70 ng/spot (MKT, LEV)

  

35

Several chromatographic methods estimate Levocetirizine and Montelukast Sodium levels in combined dosage forms. This review covers the chromatographic methods that have been developed from the year 2010 to 2020. After studying various chromatographic methods designed for estimating Levocetirizine and Montelukast Sodium in combined pharmaceutical formulations, it was observed that the RP-HPLC method is the most dominant method over other chromatographic methods due to its specificity and sensitivity. Optimization of the developed analytical methods are carried out under various analytical conditions such as different mobile phase, pH is used, based on resolution, asymmetric factor, and peak area obtained for both LEV and MKT. Methods using water and methanol as mobile phase is found to be economical. Photodiode- Array Detector or PDA detector are commonly used for the detection of compounds in the wavelength range of 200-400 nm. The RP-HPLC method reported by R. Swethan Babu, et al., 2012 can be considered as the most sensitive method among all developed methods having the lowest LOD value for Levocetirizine and Montelukast Sodium, respectively. The separation was achieved using phenomex-luna 5µ C8 Column (100Å, 250 X 4.6 mm) and acetonitrile: 0.5% triethylamine in water (90:10 v/v) as an optimized mobile phase 19. The RP-UPLC method developed by J. Bharati, et al., 2015 for the estimation of Montelukast Sodium and Levocetirizine seems to be the most rapid method giving a good resolution between two drugs with the shortest run time i.e., 3.5 min and retention time i.e., 0.587min and 1.626 min respectively for Levocetirizine and Montelukast Sodium. In this method, peaks obtained were sharp and had clear baseline separation for both drugs.

The column used was AQUITY BEH Phenyl column (50mm x 2.1mm, 1.7µm) and Potassium dihydrogen phosphate (2.72 gm) to 1 L of Milli Q water was used as mobile phase with a flow rate of 0.4 mL/min 30. Due to low solvent consumption and rapidity of the method with increased sensitivity and selectivity, we can conclude that the RP-UPLC is the most appropriate method and should be considered major method for their determination as it seems to be more beneficial than RP-HPLC and HPTLC techniques. The high recovery values in the HPTLC method indicate the suitability of the developed method for the determination of Levocetirizine and Montelukast Sodium in the combined pharmaceutical dosage form. An ideal Rf value has been obtained in HPTLC methods published by Ambadas Rote et al., 2011 and Atul S Rathore et al., 2010 23, 25. In addition to method development, a force degradation study was carried out in the work reported by Deshpande et al.2016 and Jitendra K. Sonawane et al., 2020 to check the specificity and stability of the drugs 28, 32. Both drugs were subjected to stress conditions of oxidation, photolysis, acid hydrolysis, base hydrolysis, and thermal degradation. The degradation products obtained in both methods were resolved indicating the specificity of the developed analytical methods.

Analytical Methods for estimation of Montelukast Sodium with Other Drugs in Combined Dosage form: Other than Levocetirizine, Montelukast Sodium is available in the market with many other drugs in the combined pharmaceutical formulation. Doxofylline, Fexofenadine Hydrochloride, Theophylline, Ebastine, Bambuterol Hydrochloride, Loratadine were the most common drugs found in combination with Montelukast Sodium. Both spectrophotometric and chromatographic methods for simultaneous determination of Montelukast with these drugs have been studied and summarized in Table 3.

TABLE 3: ANALYTICAL METHODS FOR ESTIMATION OF MONTELUKAST SODIUM

Sl. no. Drug combination Method Descriptions Ref.
1. Montelukast Sodium and Doxofyllinein Tablet Dosage Form HPLC Column: C18 analytical column (150 mm × 4.6 mm, 5𝜇𝜇m) Mobile phase: Methanol: phosphate buffer (10:90) Flow rate: 1.0 mL/min Detection wavelength: 280 nm Run time: 20 min Retention time: 4.78 min (MKT) 1.97 min (DOX) Linearity range:0.005-0.015 mg/mL (MKT) 0.2-0.6 mg/mL (DOX)  r2 value: 0.9941 (MKT) 0.9935 (DOX) % Purity: 99.8 %-100.3%  

36
2. Montelukast

Sodium and Fexofenadine Hydrochloride in

Tablet Dosage Form

 RP-HPLC Column: X-bridge C18 column (250 mm x 4.6 mm, 5 mm)

Mobile phase: Sodium acetate buffer: acetonitrile: methanol (25:35:40) Flow rate: 1.0 mL/min Detection wavelength: 210 nm Retention time: 3.43 min (MKT) 8.22 min (FEX) Linearity range: 12.5-37.5 mg/mL (MKT) 150-450 mg/mL (FEX) r2 value: 0.9997(MKT) 0.9994 (FEX) % RSD (Accuracy, Precision): less than 2 % % Purity: 99.73 % (MKT) 100.06 % (FEX)

  

37
3. Montelukast Sodium

and Fexofenadine Hydrochloride in Tablet Dosage Form

 Simultaneous

equation method

 Solvent: Methanol Detection wavelength: 259.60 nm 283.00 nm

Linearity Range: 30-120 mg/mL(FEX) 6-20 mg/mL(MKT)

r2 value: 0.9927 (FEX) 0.9985 (MKT) %RSD (Accuracy, Precision): less than 2 %

  

38
4.

 

 

 

 Theophylline

and Montelukast Sodium in Tablet Dosage Form

 RP- HPLC Column:ODS C- 18 Kromacil column (250 mm × 4.60 mm) Mobile Phase: Methanol Detection Wavelength: 210nm Retention time: 4.173 min (TPH) 2.910 min (MKT)  r2 value: 0.9960 for both API %RSD (Accuracy, Precision): less than 2 %  

39
5. Montelukast Sodium and Ebastine inTablet DosageForm Absorbance correction method Solvent: Methanol Detection wavelength: 345 nm, 253 nm

Linearity range: 5-25 μg/mL for both drugs r2 value:0.9993 at 345 nm  0.9999 at 253 nm %RSD (Accuracy, Precision): less than 2 % % Purity:99.75 (MKT) 99.89 (EBA)

  

40
6. Montelukast Sodium and

Bambuterol Hydrochloride in Tablet Dosage Form

 Dual wavelength method Solvent: Chloroform Detection wavelength:322.0 nm (MKT) 266.0 nm(BAM) Linearity range: 10-80 μg/mL for MKT

40-240 μg/mL for BAM r2 value:0.9997 (BAM) 0.9998 (MKT)

% Recovery: 98.9 %-99.2 %  %RSD (Accuracy, Precision): less than 2 %

  

41
7. Montelukast Sodium and Loratadinein Tablet Dosage Form

 

 HPLC Column: Symmetry C18 column Mobile phase: Sodium phosphate buffer: acetonitrile (20:80, v/v) Flow rate: 1.0 mL/min.  Detection wavelength: 225 nm Internal standard:5-Methyl 2-nitrophenol Linearity range: 100-600mg/mL (MKT)

116-580mg/mL (LTD) r2 value: less than 1 %RSD (Accuracy, Precision): less than 2%

  

42
8. Montelukast and Ebastine in Tablet Dosage Form RP-HPLC Column: Grace Smart RP C18 column (250 mm × 4.6 mm I.D. 5µ particle size) Mobile phase: Methanol: water  (0.1% triethylamine) (90:10) Flow rate: 1.2 mL/min Detection wavelength: 246 nm Retention time: 2.36 min (MKT)

4.90 min (EBA) Linearity range: 5-15 µg/mL(MKT, EBA) r2 value: 0.999

  

43
9. Bambuterol

Hydrochloride and Montelukast Sodium in Tablet Dosage Form

 RP-UPLC Column: BEH C18 Acquity UPLC column(100×2.1 mm, 1.7 μ)

Mobile phase: 0.025% (v/v) trifluoroacetic acid in water and acetonitrile  Detection wavelength: 210 nm Flow rate: 0.3mL/min Run time: 6.0 min Retention time: 1.40 min (BAM) 3.42 min (MKT) Linearity range: 6.25‑37.5 µg/mL for both drugs r2 value:0.999 % Recovery: 99.1‑100.0% (BAM)

98.0‑101.6% (MKT)

  

44
10. Montelukast Sodium and FexofenadineHydrochloride in Tablet Dosage Form RP-HPLC Column: Lichrospher® 100RP-18e column Mobile phase: Methanol:0.1% o-phosphoric acid (90:10 v/v) Flow rate: 1 mL/min  Detection wavelength: 226 nm  Retention time: 10.16 min (MKT) 12.03 min (FEX) Linearity range: 2-10 µg/mL (MKT) 24-120 µg/mL (FEX) % Recovery: 99.09, 99.81% (MKT, FEX)  

45
11. Fexofenadine Hydrochloride and Montelukast Sodium in Tablet Dosage Form Simultaneous equation method Solvent: 0.1N NaOH Detection wavelength: 259 nm (λ max of FEX) 344.5 nm (λ max of MKT) Linearity range: 50- 180 µg/mL(FEX) 1-35 µg/mL(MKT) r2 value: 0.998 % Purity: 101.88 % (FEX) 100.07 % (MKT)  

46

Analytical Methods for estimation of Levocetirizine with Other Drugs in Combined Dosage form: Levocetirizine (as Levocetirizine Hydrochloride and Levocetirizine Dihydrochloride) is available with many other drugs such as Diethylcarbamazine, Ambroxol, Pseudoephedrine, Phenylephrine Hydrochloride, Phenyl-propanolamine Hydrochloride in the combined pharmaceutical formulation Table 4.

Represents both spectrophotometric and chromatographic methods designed for the simultaneous estimation of Levocetirizine with these drugs in the combined dosage form.

TABLE 4: ANALYTICAL METHODS FOR ESTIMATION OF LEVOCETIRIZINE

Sl. no. Drug combination Method Description Ref.
1. Diethylcarbamazine and Levocetirizine Dihydrochloride in Tablet Dosage Form RP-HPLC Column: Princeton Sphere-100C18column (250×4.6 mm. 5 µ)

Mobile phase: Potassium dihydrogen orthophosphate buffer: acetonitrile (50:50 v/v) Internal standard: Losartan potassium

Flow rate: 1 mL/min Detection wavelength: 224 nm Elution time: 2.12 min (DEC) 4.27 min (LEV) Linearity range: 5 to 30 µg/mL for DEC  0.1 to 1 µg/mL for LEV

r2 value: 0.9949 for DEC 0.9979 for LEV

  

47
2. Ambroxol and Levocetirizine in Tablet Dosage Form RP-HPLC Column: Phenomenex C18 column (150 × 4.6 mm, 5µ)

Mobile Phase: 0.01M Potassium dihydrogen orthophosphate: Acetonitrile (60:40 v/v) Flow rate: 1 ml/min

Detection wavelength: 230nm Retention time: 3.60min (LEV)

4.68min (AMB) Linearity range:12-120 μg/mL for AMB 1-10μg/mL for LEV r2 value: 0.9991 for both drugs % Purity: 100.2 %, 98.2 % (AMB, LEV)

  

48
3. Levocetirizine and Pseudoephedrine in Tablet Dosage Form Simultaneous equation method Solvent: Distilled water Detection wavelength:231 nm, 257 nm

Linearity range:5-30 μg/mL (LEV) 120-960 μg/mL (PSEUDO)

r2 value: 0.9992 (LEV) 0.9991 (PSUEDO) % Purity: 100.03 % (LEV) 100.31 % (PSUEDO) % RSD (Accuracy, Precision): less than 2 %

  

49
4. Levocetirizine and Pseudoephedrine in Tablet Dosage Form Absorbance ratiomethod Solvent: Distilled water Detection wavelength:  231 nm, 257 nm

Linearity range: 5-30 μg/mL (LEV) 120-960 μg/mL (PSEUDO)

r2 value: 0.9994 (LEV) 0.9993 (PSUEDO) % Purity: 101.81 (LEV) 100.04 (PSUEDO) %RSD (Accuracy, Precision): less than 2 %

  

49
5. Levocetirizine Dihydrochloride and Phenylephrine

Hydrochloride in Tablet Dosage Form

 First-order derivative spectrophotometric method Solvent: Methanol Detection wavelength: 240nm, 283.2nm

Linearity range:4–24 𝜇g/mL (LEV) 8–48 𝜇g/mL (PHE) r2 value: 0.9964 ,0.9972 (LEV, PHE) % Purity:  Levocet-D: 99.66 % (LEV, PHE) Rinostat-L: 99.63 %, 100.3 % (LEV, PHE)

%RSD (Accuracy, Precision): less than 2 %

  

50
 

6.

 Levocetirizine and Phenylephrine in Tablet

Dosage Form

 RP-HPLC Column: C18 analytical column Mobile phase: Phosphate buffer: Methanol: Acetonitrile (40:20:40) Flow rate: 1mL/min

Detection wavelength: 231 nm. Retention time:2.85min (PHE)

6.51 min (LEV) Linearity range: 2-10 µg/mL (LEV) 5-25 µg/mL (PHE) %RSD (Accuracy, Precision): less than 2 %  % Recovery: 99.5 % (LEV) 101.1 % (PHE)

  

51
7 Levocetirizine and Phenylephrine

Hydrochloride in Tablet Dosage Form

 RP-HPLC Column: Luna 5u C18column (20mm X 4mm) Mobile phase: Methanol: potassiumdihydrogen phosphate buffer(70:30) Detection wavelength: 251nm Flow rate: 1.0 mL/min

Retention time: 8.42 min (LEV)  2.70 min (PHE)

Linearity range: 30 -150% r2 value:0.9984, 0.9983 (LEV, PHE)

% Recovery: 100.64 % (LEV) 100.40 % (PHE)

  

52
8. Ambroxol Hydrochloride and Levocetirizine

Dihydrochloride in Tablet Dosage Form

 Simultaneous equation method Solvent: Distilled water Detection wavelength: 242 nm, 231 nm

Linearity range:10-50 µg/mL (AMB) 8-24 µg/mL (LEV)

r2 value: 0.999 for both API % Recovery: 99.13 to 99.52% (AMB) 98.88 to 99.42% (LEV) %RSD (Accuracy, Precision): less than 2 %

  

53
9. Levocetirizine and Phenylpropanolamine HydrochlorideTablet Dosage Form RP-HPLC Column: Phenomenex Luna C18 column (25 cm × 4.6 mm i.d., 5 μ)  Mobile phase: Acetonitrile: 0.5%triethylamine (70:30 v/v)

Flow rate: 1.2 mL/min Detection wavelength: 220 nm

Retention time: 1.8 min (PPA) 2.6 min (LEV) % Recovery: 98.17- 103.56 % (PPA) 98.893 to 10.422 % (LEV)

  

54
10 Levocetirizine hydrochloride and Phenylephrine Hydrochloride in Tablet Dosage Form First-order derivative method Solvent: Methanol Detection wavelength: 216 nm, 230 nm

Linearity range: 3-9μg/mL (LEV) 6-18 μg/mL (PHE)

r2 value: 0.9993 (LEV) 0.9996 (PHE) % RSD (Precision, Accuracy): less than 2 %  % Purity: 99.19 % (PHE) 99.88 % (LEV)

  

55
11. Levocetirizine and Phenylephrine in Tablet Dosage Form RP-HPLC Column: Eclipse Plus C18 column (4.6 mm × 150 mm)

Mobile phase: Methanol: water (50:50 v/v)  Flow rate: 1 mL/min Detection wavelength: 277 nm Retention time: 3.37 min (LEV) 6.40 min (PHE) Linearity range: 5-25µg/mL (LEV) 2.5-12.5µg/mL (PHE) r2 value: 0.999

 56

Analytical Methods for estimation of Levocetirizine and Montelukast Sodium with Other Drugs in Combined Dosage form: For simultaneous determination of Montelukast Sodium and Levocetirizine combined with other drugs have been studied and summarized in Table 5.

TABLE 5: ANALYTICAL METHODS FOR ESTIMATION OF LEVOCETIRIZINE AND MONTELUKAST SODIUM

Sl. No Drug Combination Method Description Ref.
1. Montelukast Sodium, Levocetirizine Dihydrochloride and Acebrophylline in Tablet Dosage Form RP-HPLC Column: Hypersil ODS C18 column (250 × 4.6 mm, 5µm) Mobile phase: Methanol, acetonitrile and 20 mM ammonium acetate buffer (60:30: 10v/v) Flow rate: 0.8 mL/min  Elution time: 10 min Linearity range: 2-12 µg/mL for MKT and LEV 20-120µg/mL ABP r2 value: 0.999 % Purity: 99.89(LEV) 100.30%(ABP) 100.59% (MKT) % RSD (Precision, Accuracy): less than 2 %  

57
2. Ambroxol, Montelukast, and Levocetirizine in Tablet Dosage Form RP-HPLC Column: C18 column  Mobilephase: Triethylamine buffer: ACN: methanol (20:30:50v/v)  Detection wavelength: 280 nm  Linearity range: 7.7-22.5 µg/mL (AMB) (r 2=0.999)  1.25-3.75 µg/mL (MKT) (r2=0.998)

5-15 µg/mL (LEV) (r2=0.997) % Purity: 98.81% (AMB) 102.56% (MKT) 98.6 % (LEV)

  

58
3. Acebrophylline, Montelukast and Levocetirizine DihydrochlorideForm Simultaneous equation method Solvent: Methanol Detection wavelength:250.14 nm ((λ max of ABP) 284.79 nm((λ max of MKT) 231.27 nm ((λ max of LEV) Linearity range: 6-18 μg/mL (ABP, MKT) 3- 12μg/mL for (LEV) r2 value: 0.999 for all drugs % Purity: 100 % (ABP) 101 % (MKT) 99 %(LEV) % RSD (Precision): less than 2 %  

59
4. Doxofylline, Montelukast, and Levocetirizine Dihydrochloride in Tablet Dosages Form RP-HPLC Column: C18 (150 x 250 x 4.6 mm) Agilent column

Mobile phase: Ammonia acetate Buffer: ACN) pH 3.5

Retention time: 4.425 min (DOX) 7.409 min (MKT)

8.558 min (LEV) Linearity range: 10-15 µg/mL for all drugs r2 value: less than 1 % Purity: 101.21 % (DOX)

98.90 % (MKT) 100.40 % (LEV)

  

60

CONCLUSION: In recent years, various analytical methods have reported various analytical methods for quantitative estimation of drugs in combined pharmaceutical dosage forms under spectrophotometric and chromatographic methods. This article provides a summary of reported analytical methods for simultaneous estimation of Levocetirizine and Montelukast Sodium in bulk, combined pharmaceutical formulation, and a combination of these drugs with other different drugs available in the market. The literature review reveals that RP- HPLC is the most frequently used method over different spectroscopic methods and other chromatographic methods for their determination. RP-UPLC with a PDA detector gives good resolution between two drugs and is the most rapid analytical method for determining pharmaceutical compounds. Therefore, we can conclude that RP-UPLC and RP-HPLC should be the most preferred method for the simultaneous estimation of Montelukast sodium and Levocetirizine in terms of sensitivity, rapidity, and reliability. Spectrophotometric methods are economical, non-sophisticated, show a high level of accuracy and precision, and can be used as an alternative method to overcome the demerits of Chromatographic methods, which are complex, time-consuming, require expensive setup, and require a skilled operator. Overall, both spectrophotometric and chromatographic methods can be successfully used to simultaneously estimate the pharmaceutical drug product in bulk and combined pharmaceutical dosage form. All the developed methods for Levocetirizine and Montelukast Sodium were validated per ICH guidelines, and the methods met its acceptance criteria.

ACKNOWLEDGEMENT: We take this opportunity to express our profound gratitude to Dr. H. P Chhetri, Director, and Dr. Abhinay Chhetri, Associate Director, Himalayan Pharmacy Institute, for providing all the facilities required for the completion of this work.

CONFLICTS OF INTEREST: No conflict of interest between any of the authors.

REFERENCES:

  1. Vairagi KP and Desai SP: A review on analytical method development for simultaneous estimation and validation of Montelukast Sodium and Bilastine. World Journal of Pharmaceutical Research 2021; 10(4): 665–78.
  2. Kumar SB and Rao SB: A validated stability-indicating and LC-MS compatible method for the determination of related substances and an assay of Montelukast Sodium and Levocetirizine HCl by U-HPLC in the tablet dosage form. Indo American Journal of Pharmaceutical Sciences 2018; 5(3): 1368–82.
  3. Ali S and Gupta M: Method development and validation for the simultaneous estimation of Montelukast Sodium and Levocetirizine Hydrochloride tablet using RP-HPLC. Journal of Pharmaceutical Sciences and Research 2019; 11(8): 2998-3000.
  4. Sakur AA, Nashed D and Noureldin I: Green Potentiometric determination of some of the third-generation antihistamines: Fexofenadine, Desloratadine, and Levocetirizine by using new carbon paste electrodes. Talanta Open 2022; 100116.
  5. Sherif OE, Issa YM and Abo-Dena AS: β-correction and extraction to overcome spectral overlap in spectrophotometric determination of Levocetirizine Dihydrochloride. International Journal of Research in Pharmacy and Chemistry 2014; 4(1): 181-91.
  6. Agha DS, EL-zien HI. Solid state compatibility studies between Montelukast Sodium and Levocetirizine. Asian Journal of Pharmaceutical and Clinical Research 2018; 11(3): 368-74.
  7. Indian Pharmacopoeia. The controller of publication. New Delhi 2007; 2: 1290.
  8. Indian Pharmacopoeia. The Indian Pharmacopoeia Commission Ghaziabad 2014; 2: 2247- 2248.
  9. British Pharmacopoeia. The Stationery Office; London 2015; 2: 317-319.
  10. S. Pharmacopoeia-National Formulary. Rockville, VolIII. 2015: 4930-4938.
  11. Kumar NR and Vaidhyalingam V: Development and validation for the simultaneous quantificatio of Montelukast and Levocetirizine by UV, RP-HPLC, and HPTLC methods in tablets. International Journal of Pharmacy and Analytical Research 2016; 5(3): 487-96.
  12. Bylappa K and CR WD: Evaluation of efficacy of fixed dose combination of montelukast and levocetirizine compared to monotherapy of Montelukast and Levocetirizine in patients with seasonal allergic rhinitis. International Journal of Otorhinolaryngology and Head and Neck Surgery 2018; 4(2): 467.
  13. Sawale VS and Umamaheshwari D: A Review on Novel Analytical Techniques Used in Method Development and Validation of Pharmaceuticals. Journal of Pharmaceutical Sciences and Research 2020; 12(2): 321-8.
  14. [Mittal M, Upadhyay Y, Anghore D, Kumar A and Rawal RK: Simultaneous estimation of Acebrophylline, Montelukast, and Levocetirizine Dihydrochloride in marketed formulation by high- performance liquid chromatography method. Pharma Aspire 2018; 10(1): 23-8.
  15. Sharma S, Singh N, Ankalgi AD, Rana A and Ashawat MS: Modern Trends in Analytical Techniques for Method Development and Validation of Pharmaceuticals: A Review, Journal of Drug Delivery and Therapeutics 2021; 11(1): 121-130.
  16. Sankar ASK, Baskar GN, Nagavalli D, Anandakumar K and Vetrichelvan T: Simultaneous estimation of Montelukast Sodium and Levocetirizine Hydrochloride from tablet dosage form. Research Journal of Pharmacy and Technology 2009; 2(4): 743-5.
  17. Choudhari V, kale A, Abnawe S, Kuchekar B, Gawli V and Patil N: Simultaneous determination of Montelukast Sodium and Levocetirizine Dihydrochloride in pharmaceutical preparations by Ratio Derivative Spectroscopy. International Journal of Pharm Tech Research 2010; 2(1): 4-9.
  18. Nilam PK and Pancholi S: Determination of Montelukast Sodium and Levocetirizine Dihydrochloride in tablet dosage form by AUC Curve method. Der Pharma Chemica 2011; 3(5): 135-40.
  19. Babu RS, Bharadwaj KA, Arjun NC, Nagaraj and Prasad V: A validated comparitative LC and Ratio First Derivative Spectrophotometric method for the simultaneous determination of Levocetirizine Dihydrochloride and Montelukast Sodium in bulk and pharmaceutical dosage forms. Journal of Applied Pharmaceutical Science 2012; 2(8): 243–9.
  20. Patel NK, Chouhan P, Paswan SK and Soni PK: Development and validation of a UV Spectrophotometric method for simultaneous estimation of combination of Montelukast Sodium in presence of Levocetirizine Dihydrochloride. Der Pharmcia Lettre 2014; 6(3): 313-21.
  21. Tamilselvi N, Mohamed ASH, Basheer C and Louis NL: Development and validation of Spectro-photometric method for simultaneous determination of Montelukast Sodium and levocetirizine Hydrochloride. Journal of Pharma Innovative Research 2015; 2(1): 6-10.
  22. Rashed NS, Abdallah OM and Said NS: Development and validation of Spectrophotometric methods for simultaneous determination of Levocetirizine Dihydrochloride and Montelukast Sodium in tablet dosage form. World Journal of Pharmacy and Pharmaceutical Sciences 2015; 4(5): 73-88.
  23. Rote AR and Niphade VS: Determination of Montelukast Sodium and Levocetirizine Dihydrochloride in combined tablet dosage form by HPTLC and First-Derivative Spectrophotometry. Journal of Liquid Chromatography and Related Technologies 2011; 34: 155–67.
  24. Somkuwar S and Pathak AK: Simultaneous estimation of Levocetirizine Dihydrochloride and Montelukast Sodium by RP-HPLC method. Pharmacia 2012; 1: 90-4.
  25. Rathore AS, Sathiyanarayanan L and Mahadik KR: Development of Validated HPLC and HPTLC Methods for simultaneous determination of Levocetirizine Dihydrochloride and Montelukast Sodium in bulk drug and pharmaceutical dosage form. Pharmaceutica Analytica Acta 1: 106.
  26. Ishaq BM, Prakash KV, Mohan GK, Muneer S and Ahad HA: RP-HPLC Method for simultaneous estimation of Levocetirizine Dihydrochloride and Montelukast Sodium in tablets. Indian EJ. Pharma Sciences 2015; 1(01): 18-20.
  27. Rao L, Raja T, Rao AL. Development and validation of a reversed phase HPLC method for simultaneous determination of Levocetirizine and Montelukast Sodium in tablet dosage form. International Journal of Research in Pharmacy and Chemistry 2012; 2(4): 1057-63.
  28. Sonawane JK, Patil DA, Jadhav BSL, Jadhav SL and Patil PB: Stability Indicating RP-HPLC method development and validation for simultaneous quantification of antihistaminic & anti-asthmatic drug in bulk and tablet dosage form. Journal of Pharmaceutical and Biological Sciences 2020; 8: 12–22.
  29. Basu A, Basak K, Chakraborty M and Rawat IS: Simultaneous RP-HPLC estimation of Levocetirizine Hydrochloride and Montelukast Sodium in tablet dosage form. International Journal of Pharm Tech Research 2011; 3(1): 405-10.
  30. Bharati J, Naidu BC, Sumanth M and Rajana N: A rapid, RP-UPLC assay method for simultaneous determination of Montelukast Sodium and Levocetirizine Dihydrochloride in pharmaceutical dosage forms. World Journal of Pharmacy and Pharmaceutical Sciences 2015; 4(11): 1409-21.
  31. Sharma S, Sharma MC, Kohli DV and Sharma AD: Development and validation of TLC-Densitometry method for simultaneous quantification of Montelukast Sodium and Levocetirizine Dihydrochloride pharmaceutical solid dosage form. Der Pharmacia Lettre 2010; 2(1): 489-94.
  32. Bhatt J, Deshpande P, Deore N, Gandhi Y and Sarowar G: Stability indicating method development and validation for simultaneous determination of Levocetirizine Hydrochloride and Montelukast Sodium as bulk drugs and in tablet dosage form. World Journal of Pharmaceutical Research 2016; 5: 644–55.
  33. Naaz A and Vani R: Simultaneous estimation of Montelukast and Levocetirizine in its bulk and liquid dosage form by RP-HPLC. Indo American Journal of Pharmaceutical Research 2015; 5: 3338-47.
  34. Venila Rani K and Padmalatha H: Method development and validation for the simultaneous estimation of Montelukast and Levocetirizine in pharmaceutical dosage form by using RP HPLC. International Journal of Pharmacy 2015; 5(2): 631–6.
  35. Konam K, Prashad PH, Lukaraju PS, A SM, Fareedullah M and Imtiaz M: Determination of Montelukast Sodium and Levocetrizine Hydrochloride by using HPTLC method. Elixir International Journal 2011; 38: 4276-78.
  36. Nirupa G, Siva Kumar A and Tripathi UM: Novel LC method development and validation for simultaneous determination of Montelukast and Doxofylline in bulk and pharmaceutical dosage forms. Journal of Chemistry 2013; 2013.
  37. Vekaria H, Muralikrishna KS and Sorathiya M: Development and validation of HPTLC method for simultaneous estimation of Montelukast Sodium and Fexofenadine Hydrochloride in combined dosage form. Der Pharmacia Lettre 2012; 4: 755–62.
  38. Patle D and Nagar S: UV-visible spectrophotometric estimation of Montelukast and Fexofenadine by simultaneous equation method in bulk & combined tablet dosage form. Current Trends in Biotechnology and Pharmacy 2017; 11(4): 382-8.
  39. Jain P, Rajoriya V and Kashaw V: Development and validation of simultaneous RP-HPLC method for the estimation of Theophylline and Montelukast in pharmaceutical formulation. Analytical Chemistry Letters 2015; 5: 172–82.
  40. Patel NN, Rana NS, Rajesh KS, Patel PR, Limbachiya U and Pasha TY: Spectrophotometric method for simultaneous estimation of Montelukast Sodium and Ebastine in bulk and their combined tablet dosage form. Indian Journal of Pharmaceutical Education and Research 2014; 48: 87–91.
  41. Patel DJ, Patel SA and Patel SK: Simultaneous determination of Montelukast Sodium and Bambuterol Hydrochloride in tablet dosage form by Ultraviolet Spectrophotometry (Dual Wavelength Method). International Journal on Pharmaceutical and Biomedical Research 2010; 1(3): 71-5.
  42. Radhakrishna T, Narasaraju A, Ramakrishna M and Satyanarayana A: Simultaneous determination of Montelukast and Loratadine by HPLC and Derivative Spectrophotometric methods. Journal of Pharmaceutical and Biomedical Analysis 2003; 31(2): 359–68.
  43. Ambadkar SG, Dewani AP, Bakal RL and Chandewar AV: An isocratic HPLC method for simultaneous determination of Montelukast and Ebastine in pharmaceutical formulations. International Journal of Drug Formulation and Research 2013; 4(3): 123-40.
  44. Yanamandra R, Vadla CS, Puppala UM, Patro B, Murthy YLN and Parimi AR: Development and validation of a rapid RP-UPLC method for the simultaneous estimation of Bambuterol Hydrochloride and Montelukast Sodium from tablets. Indian J of Pharma Sciences 2012; 74(2): 116-21.
  45. Pankhaniya M, Patel P and Shah JS: Stability-indicating HPLC method for simultaneous determination of Montelukast and Fexofenadine Hydrochloride. Indian Journal of Pharmaceutical Sciences 2013; 75(3): 284-90.
  46. Sowjania G and Sastri T: UV Spectrophotometric method development and validation for simultaneous determination of Fexofenadine Hydrochloride and Montelukast Sodium in tablets. World Journal of Pharm Pharm Sci 2018; 6(10): 780-9.
  47. Mahesh Reddy J, Jeyaprakash MR, Madhuri K, Meyyanathan SN and Elango K: A sensitive RP-HPLC method for simultaneous estimation of Diethylcarbamazine and Levocetirizine in tablet formulation. Indian Journal of Pharmaceutical Sciences 2011; 73: 320–3.
  48. Kumar S, Gautam D and Talwan P: Method development and validation for the simultaneous estimation of in Ambroxol and Levocetirizine bulk and pharmaceutical dosage form by using RP-HPLC method. International Journal of Research in Pharmacy and Chemistry 2020; 10(1): 22-7.
  49. Merukar SS, Mhaskar PS, Bavaskar SR, Burade KB and Dhabale PN: Simultaneous spectrophotometric methods for estimation of Levocetirizine and Pseudoephedrine in pharmaceutical tablet dosage form. Journal of Pharmaceutical Sciences and Research 2009; 1(2): 38-42.
  50. Parmar K, Baldania S, Shah D, Chhalotiya U and Parmar N: Development and validation of First-Order Derivative Spectrophotometry for simultaneous determination of Levocetirizine Dihydrochloride and Phenylephrine Hydrochloride in pharmaceutical dosage form. International Journal of Spectroscopy 2013; 2013: 1–6.
  51. Suresh Ponnuru V: Rao Nr. Development and validation of a chromatographic method for simultaneous estimation of Levocetirizine and Phenylephrine in pharmaceutical dosage form. International Journal of Advances in Pharmaceutical Research 2013; 4(7): 1921-26.
  52. Pharm Med Res IJ, Bhushan B, Singh Baghel U and Singh R: RP-HPLC method development for the estimation of Levocetirizine and Phenylephrine hydrochloride in combined dosage form. International Journal of Pharmaceutical and Medical Research 2013; 1(2): 85-90.
  53. Prabu SL, Shirwaikar AA, Shirwaikar A, Kumar CD and Kumar GA: Simultaneous UV spectrophotometric estimation of Ambroxol Hydrochloride and Levocetirizine Dihydrochloride. Indian Journal of Pharmaceutical Sciences 2008; 70(2): 236–8.
  54. Srinivasan A, Divakar P, Maheswaran A, Saravanan D and Info A: Simultaneous determination of Levocetrizine and Phenylpropanolamine Hydrocholride by RP-HPLC. International Journal of Research in Pharmaceutical Sciences and Technology 2020; 2: 32–6.
  55. Deshmukh VV, Wagh DD, Vassa SP and Gujar KN: Development of First Order Derivative Ultraviolet Spectrophotometric method for simultaneous estimation of Levocetirizine Hydrochloride and Phenylephrine Hydrochloride in bulk and combined dosage form. International Research J of Pharmacy 2013; 4: 115–9.
  56. Thejomoorthy K: HPLC Method Development and Validation for the simultaneous estimation of Levocetirizine and Phenylephrine in Bulk and Pharmaceutical Dosage Form. International Journal of Pharmacognosy and Chemistry 2020; 19-30.
  57. Butala S and Khan T: Development and validation of RP-HPLC method for simultaneous estimation of Montelukast Sodium, Levocetirizine Dihydrochloride and Acebrophylline in fixed dose combination tablets. International Journal of Pharmaceutical Sciences and Research 2021; 12(9): 4851-57.
  58. Suthakaran R, Shankar CH and Sudha P: A New analytical method development and validation of Ambroxol, Montelukast and Levocetirizine in Tablet dosage form by RP-HPLC method. International Journal of Biomedical Investigation 2018; 1: 108.
  59. Mittal M, Upadhyay Y, Anghore D and Rawal RK: Simultaneous estimation of Acebrophylline, Montelukast and Levocetrizine Dihydrochloride in marketed formulation by UV-spectroscopy. World Journal of Pharmacy and Pharmaceutical Sciences 2016; 5: 1274-84.
  60. Kumar N, Anghore D, Rawal RK and Pandey A: RP-HPLC and UV method development for simultaneous estimation of Doxofylline, Montelukast, and Levocetirizine Dihydrochloride in pharmaceutical dosages form. Analytical Chemistry Letters 2018; 8(2): 195-204.

    How to cite this article:

    Bhutia YD, Bhuyan NR, Shrestha B and Baraily VR: A review on analytical methods for estimation of levocetirizine and montelukast sodium in combined pharmaceutical dosage forms. Int J Pharm Sci & Res 2022; 13(12): 4871-84. doi: 10.13040/IJPSR.0975-8232.13(12).4871-84.

    All © 2022 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.

Article Information

8

4871-4884

822 KB

824

0

English

IJPSR

Y. D. Bhutia, N. R. Bhuyan, B. Shrestha and V. R. Baraily *

Department of Pharmaceutical Analysis, Himalayan Pharmacy Institute, Majhitar, East Sikkim, India.

Vishalahpi21@gmail.com

26 March 2022

24 June 2022

13 September 2022

10.13040/IJPSR.0975-8232.13(12).4871-84

01 December 2022

Download