Method Validation for the Quantification of Dexlansoprazole dual-delayed release capsules by RP-HPLC

 

Lakshmi Narasimha Rao Regana¹*, A. Krishna Manjari Pawar²

¹Research Scholar, Department of Pharmaceutical Analysis, A.U College of Pharmaceutical Sciences,

Andhra University, Visakhapatnam, Andhra Pradesh, India - 530003.

²Associate Professor, Department of Pharmaceutical Analysis, A.U College of Pharmaceutical Sciences,

Andhra University, Visakhapatnam, Andhra Pradesh, India - 530003.

 

ABSTRACT:

Dexlansoprazole is used in the symptomatic management associated with Gastroesophageal Reflux Disease and Erosive Esophagitis. It is a new generation proton-pump inhibitor. The main aim of this article is to develop and validate an RP-HPLC method for the estimation of Dexlansoprazole in both 20%W/W dual delayed-release pellet and dual delayed-release capsule forms 60 mg. The foundational work facilitated the validation of a newly developed RP-HPLC method for the quantitative of Dexlansoprazole. Method was achieved with Inertsil ODS C18, 100x4.6mm, 5µm at 1.0ml/min flow rate for 10min run time at 285nm. The linearity was achieved in the range of 15-120ppm with R² value 1.000 and retention time at 4.53min. Accuracy was found to be 98-102% with a precision %RSD of 0.07. This method is designed to be simple, precise, and economical, featuring a shorter run time that makes it ideal for routine quality control applications. The validation was performed in compliance with ICH guidelines, confirming that the established method is reliable for quality control purposes.

 

 

 

1. INTRODUCTION:

Dexlansoprazole is a new generation proton pump inhibitor. It is used to manage the symptoms of Gastroesophgeal reflux disease and Erosive         Esophagitis^1-13. As compared to Omeprazole, Lansoprazole and Pantoprazole, Dexlansoprazole possess an unique pharmacokinetic profile with its dual delayed release delivery system. 

 

Thie drug inhibits final step in the production of gastric acid by blocking (H+, K+) ATPase enzyme ^14-25. It has white to near white crystalline powder with the chemical formula ^{C16H14F3N3O2S}. The IUPAC name of Dexplansoprazole is 2-[(R)-[3-methyl-4-(2,2,2-trifluoroethoxy) pyridine-2-yl]-1H-benzimidazole with molecular weight of 369.40gm/mol. This drug is freely soluble in methanol, ethanol, dimethylformamide and ethyl acetate; soluble in acetonitrile; slightly soluble in ether; very slightly soluble in water and practically insoluble in hexane^26-35.

 

Figure 1. Chemical Structure of Dexlansoprazole

This comprehensive literature review^36-51 investigates the physicochemical properties of Dexlansoprazole in both pellet and capsule formulations 60 mg and presents various analytical methodologies employed for its quantification. This foundational work facilitated the validation of an innovative reverse-phase high-performance liquid chromatography (RP-HPLC) method for the quantification of Dexlansoprazole. The validation process adhered to ICH Q2 guidelines⁵² concerning the validation of analytical procedures and ICH Q14 guidelines for analytical procedure development, thereby affirming its applicability for the intended purpose.

 

2. EXPERIMENTAL WORK:

2.1   MATERIALS AND METHODS.

i) Chemicals, Reagents and Solvents:

Acetonitrile of HPLC grade was purchased from Merck, Mumbai. Water of HPLC grade was prepared from Millipore milli-Q water purification system was used throughout the process. Analytical grade chemicals include sodium hydroxide, and Ammonium acetate were purchased from E. Merck Limited, Mumbai, India.

 

ii) Working Standards/Reference Standards and pharmaceutical dosage form:

The References samples and Working Standards of were provided as a gift sample from Vyshno Bio Sciences Research and Development Laboratories Hyderabadand Sainor Laboratories Private Limited, Unit – II Pharma Division located at Jeedimetla, Hyderabad, India. Dexlansoprazole capsule labeled to contain 60mg of Dexlansoprazole of Dexlanzol 60 Capsule DR purchased from local Pharmacy store.

 

Table 1. Chemicals, Reagents and Standards

Chemicals and Solvents Standards	Make	Grade	Batch No.	Assay
Milli-Q Water	-	HPLC	--	--
Acetonitrile	Merck	HPLC	T063G27	³99.90%
Ammonium Acetate	Merck	AR	L189N18	³97.60%
Sodium Hydroxide	Merck	AR	L270R90	³99.98%
Dexlansoprazole Working Standards	IHS	IHS	WS/DLP/23-001	92.89%
Dexlansoprazole Placebo Pellets	IHS	IHS	DLPP/FRD/23-009	-
Dexlansoprazole pellets 20% w/w	IHS	IHS	DLP/FRD/22-018	101.3%
Dexlansoprazole pellets 20% w/w	IHS	IHS	DLP/FRD/22-027	101.9%
Dexlansoprazole Pellets 20.0%w/w	IHS	IHS	DLPP/FRD/22-036	101.8%

 

2.1      Analytical Instrumentation and Equipments:

Table 2. Analytical Instrumentation and Equipments

S. No	Instrument	Make, Model and Details	Identification No.
1.	HPLC	Waters e2695/Alliance Series	ARD/LC/2021009
2.	HPLC-Column	Nucleosil RP8; 128 x 4.6mm 5mm	ARD/CLM/RP/0218
3.	Analytical Balance	Sartorius	ARD/BAL/201806
4.	Analytical Balance	Fisher Scientific	ARD/BAL/201927
5.	pH Meter	Thermo Scientific: ORIONSTAR A215	ARD/PHM/202103
6.	Sonicator	PCi Ultrasonic bath chiller Model	ARD/SC/2021005
7.	Refrigerator	Sanyo --G 25	ARD/SRC/RFG/06
8.	Centrifuge	REMI PR-27	ARD/REM/CTF/06
9.	Shakers and Mixers	Thermo Scientific - MaxQ™ 4450	ARD/MIX/TFS/09

 

2.2      Chromatographic Conditions:

Table 3. Chromatographic Conditions

Column	Inertsil ODS C18, 100x4.6 mm, 5µm
Flow Rate	1ml/min
lmax	2285nm
Runtime	10min
Column Temp.	25oC
Auto sampler Temp.	20oC
Injection Volume	10 mL
Elution	Isocratic
Diluent	0.1                  N NaOH Solution

 

2.3  Sample, Standards and Solutions Preparations

Solution A:

1.5gm of Ammonium acetate was weighed and dissolved in 1000ml water.

 

 

Solution B: Acetonitrile

Mobile Phase: Mixture of solution A and B was prepared in 65:35 ratio and filtered with 0.45mm membrane filter and sonicated for a while.

 

0.1N NaOH: About 2.0gm of Sodium Hydroxide was weighed into 50ml volumetric flask. Then, 400ml of water was added and diluted till the mark with water.

 

Standard solution:

About 60mg Dexlansoprazole working standard was weighed accurately into 100ml volumetric flask. Then, 25ml of 0.1N NaOH was added to dissolve the standard and it was diluted further with 0.1N NaOH and mixed well. 5ml of the above solution was taken out into 50ml volumetric flask and made till the mark with the mobile phase.

 

Sample solution:

Accurately weighed and transferred about Five capsules or the pellets about 1500mg (equivalent to 300mg of Dexlansoprazole) into volumetric flask of 500ml, 100ml 0.1N NaOH was added and sonicated for about 20 min with intermittent shaking to dissolve the contents, then it was made till the mark with mobile phase. The solution was centrifuged in the sample tubes with 5000 RPM for 10mints. 5ml of supernatant solution was taken into 50ml volumetric flask and made till the mark with mobile phase to get 60ppm concentration.

 

Blank Solution: Mobile phase.

 

Placebo solution:

Weighed and transferred the placebo pellets about 1200 mg (equivalent to 300mg Dexlansoprazole) into volumetric flask of 500ml. Then, 100ml of 0.1N NaOH was added and sonicated for 20min with intermittent shaking to dissolve the contents and made till the mark with mobile phase. Centrifugation was done for 5000 RPM for 10 minutes. The supernatant solution was collected and 5ml from this was pipetted out into volumetric flask of 50ml and diluted till the mark with mobile phase to get 60ppm concentration.

 

Linearity solutions:

The ability to obtain the test results that are directly proportional to the analyte concentration is termed as linearity. It was carried out at 25, 50, 75, 100, 125 and 200% standard concentrations.

i)     Linearity Stock Solution Preparation:

75g Dexlansoprazole working standard was weighed into volumetric flask of 100ml, and 25ml of 0.1N NaOH was added and made till the mark with the same solution.

ii)   Linearity Solution Preparation:

A standard calibration curve was established by injecting working standard solutions of Dexlansoprazole at six concentration levels: 15, 30, 45, 60, 75, and 120 ppm. The peak area responses for each concentration level were measured under the specified chromatographic conditions. Least square regression analysis was performed to relate the peak area to the concentration ratio. Unknown concentration was estimated by calibration curve or the regression equation.

 

Accuracy Solution:

Three sample solutions were prepared at specified levels15,60 and 120 ppm and injected into the system ranging from 25% to 200% of specification level using at least three replicates of minimum three concentration levels.

 

Solution stability Solution Preparation:

Stability for standard and sample was carried at bench top and refrigerator condition by injecting at regular intervals (e.g. initial hour, 12th hour, 24th hour and 48th Hours) against to fresh standard solution.

 

3. RESULTS AND DISCUSSION:

The International Council for Harmonisation (ICH) provides guidelines for validating the developed analytical methods particularly in the context of pharmaceuticals. The key parameters selected or the validation is a systematic approach to ensure that a method produces high-quality, reliable data, ultimately contributing to the safety and efficacy of pharmaceutical products.

 

Table 4. Validation Parameters

S. No	Validation Parameter
1.	Specificity and system Suitability
2.	Precision	I.      System precision
		II.      Method precision
3.	Linearity
4.	Accuracy
5.	Range
6.	Robustness
7.	Ruggedness

 

3.1      Data summary of specificity and system suitability:

Table 5. Specificity and System Suitability Summary Data

Specificity and System suitability		Results	Acceptance criteria
Specificity
Parameter	Standard Solution		RT was compared with that of the standard.
Identification and Retention Time (RT) Conformation.	Dexlansoprazole	4.53
	Sample Solution
	Dexlansoprazole	4.53
Peak Purity index		Single point threshold	Peak purity should pass. Peak purity index should be greater than single point threshold.
Standard Solution (Peak Purity)	1.0000	0.9998
Sample Solution (Peak Purity)	0.99999	0.99998
Blank and Placebo Solution. Interference	Dexlansoprazole	NIL	Blank and placebo solution should not elute any peak at the RT of analyte peak.
System suitability
% RSD for area of standard (5 replicates)		0.13	% RSD should be NMT 2.0%.
The % RSD for RT of 2 replicate injections of the DLPZ sample solution		0.12	% RSD should be NMT 1.0%.
No. of theoretical plates for standard		6123	Theoretical plates should be NLT 2000.
Tailing factor for main peak in DLPZ standard solution		1.01	The tailing factor for main peak in DLPZ standard solution shouldbe NMT 0.8 and 2.0

Figure 2. Chromatogram for Blank

 

Figure 3. Chromatogram for Placebo

 

Figure 4. Chromatogram for Standard

 

Figure 5. Chromatogram for Sample solution-1

 

Figure 6. Chromatogram for Sample solution-2

 

Table 6. System Suitability Standard Solution Dexlansoprazole

Solutions	RT	Area	Tailing factor	Theoretical plates
Standard solution injection-1	4.54	1192375	1.01	6120
Standard solution injection-2	4.54	1191633	1.02	6133
Standard solution injection-3	4.53	1190202	1.03	6048
Standard solution injection-4	4.53	1188945	1.03	5892
Standard solution injection-5	4.53	1189248	1.03	5645
Mean	4.53	1190481	1.02	5968
Standard deviation	0.0055	1489.2754	-	-
% Relative           Standard deviation	0.12	0.13	-	-
Bracketing Standard solution	4.53	1188377	1.02	5190

 

Table 7. Dexlansoprazole Sample Solution Specificity

Solutions	RT	AREA	Tailing factor	Theoretical plates
Sample solution Preparation -1	4.53	1286711	1.02	5418
Sample solution Preparation -2	4.53	1287306	1.02	5265

3.2      Precision:

Precision describes the closeness between serial measurements that were obtained from multiple sampling conditions from the homogeneous sample.

 

 

Table 8. Dexlansoprazole Precision data

System precision	Results	Acceptance limits
% RSD of the standard solution	0.07	% RSD for area f the standard solution should be NMT 2.0%
No. of theoretical plates for main peak in standard solution	5199	Theoretical plates should be NLT 2000
Tailing factor for the standard solution	1.04	Tailing factor should be NMT 2.0%
Method precision
Calculated %RSD for % Assay content DLPZ from six sample preparations	0.21	%RSD for % Assay content DLPZ from six samples preparations should be NMT 2.0 with all the individual values within limit.

 

3.2.1 System precision:

System precision describes the instrument performance under the prescribed chromatographic parameters. System precision studies were carried out by single preparation of standard solution and injecting the sample under the same conditions with six determinations.

 

3.2.2  Method Precision:

Method Precision studies were carried out with test solution of six preparations and injecting the sample under the same chromatographic conditions.

 

3.3      Linearity:

The linearity studies and regression characteristics of the developed method were depicted in the table.

 

Table 9. Linearity results of Dexlansoprazole

Concentration(ppm)	*Peak area
15 (25%)	311856
30 (50%)	613763
45 (75%)	912244
60 (100%)	1212690
75 (120%)	1518755
120 (200%)	2434534
y=- 0.2476 ; R2 = 1.000; Slope = 20213.76; F-Test = 1.001

*= Average peak area of 3 replicate injection for each concentration

 

Figure 7. Linearity Graph of Dexlansprazole

 

3.4 Accuracy:

Sample concentration levels ranging from 25% to 200% of specification level using at least three replicates of minimum three concentration levels 25, 100 and 200% were injected. The mean percent recovery and % RSD at each level was calculated. 

 

Table 10. Accuracy studies of Dexlansprazole

Accuracy Solution	Amount Found (ppm)	Amount added (ppm)	% Recovery	Average % Recovery	% RSD
25% Sample-1	15.237	15.250	99.912	99.90	0.07
25% Sample-2	15.144	15.150	99.960
25% Sample-3	15.242	15.270	99.815
100% Sample-1	60.457	60.470	99.978	99.93	0.05
100% Sample-2	60.560	60.640	99.869
100% Sample-3	60.530	60.570	99.934
200% Sample-1	120.892	120.350	100.450	100.44	0.14
200% Sample-2	120.824	120.140	100.570
200% Sample-3	120.875	120.530	100.286

 

Table 11. Robustness data of Dexlansprazole

Parameter	Optimised condition	Applied condition	Area of the peak	RT (min)	Plate Count	Tailing Factor
Flow rate ± 0.1mL/min	1mL/min	0.9 mL/min	1318068	5.03	7867	1.29
		1.1mL/min	1076398	4.15	6838	1.29
Organic Phase composition (±10%v/v)	650:350	685:315	1183009	5.38	8306	1.26
		615:385	1198191	3.01	4922	1.39
Column Temperature (±5ºC)	25 ºC	20 ºC	1187396	4.64	6994	1.30
		25 ºC	1182936	4.45	7702	1.28

 

3.5 Robustness:

Robustness is established by varying some of the parameters like flow rate, composition of Organic phase and column temperature. (Table-11).

3.6 Proposed procedures for marketed Pharmaceutical Formulation:

The Marketed Capsule (Dexilant) was analysed separately in HPLC by injecting 10µL of standard and sample solutions. Quantification of the drug was done by comparing the peak area of standard to that of the sample. The typical chromatograms values of standard and sample solutions using the proposed method are shown in table-12.

 

Table 12. Assay results in dosage form

Formulation	Batch No	Label claim(mg)	% Assay*
Dexilant Dual Delayed Release Capsule	DLP6022032	Dexlansprazole -60mg	100.58
	DLP6022033	Dexlansprazole -60mg	100.11
	DLP6022034	Dexlansprazole -60mg	99.98

*=Average assay % of 3 replicate injections of individual batch

 

SUMMARY AND CONCLUSION:

The results of the validation parameters were summarized below.

 

Table 13. Method validation summary

Parameters	Dexlansprazole
Linearity (ppm)	15 - 120
Regression equation	y = -0.2476
Slope	20213.76
Regression coefficient(R2)	1.000
Homoscedasticity (F-Test)	1.001
Precision (%RSD)	0.07
Accuracy	98.0 % - 102.0 %
Assay (% w/w)	100.58

 

CONCLUSION:

The developed HPLC method for the estimation of Dexlansoprazole in its dual delayed capsule formulation has proven to be specific, precise, reliable, robust and suitable for its intended application. Key parameters such as specificity, accuracy, precision, robustness and linearity, were all within acceptable limits, confirming the method's efficacy in quantifying Dexlansoprazole accurately.

 

The method showed excellent linearity over the specified concentration range, with high correlation coefficients. The recovery studies indicated that the method is capable of accurately measuring Dexlansoprazole without significant interference from excipients. Additionally, the precision results reflected minimal variability, underscoring the method's reliability for routine analysis.

Overall, the validated HPLC method provides a comprehensive analytical tool for the quality control of Dexlansoprazole 60 mg dual delayed release capsules, ensuring that pharmaceutical products meet regulatory standards.

 

CONFLICT OF INTEREST:

Authors declared that there was no conflict of interest.

 

ACKNOWLEDGEMENT:

Authors are thankful to the Pharmaceutical Analysis department, A.U College of Pharmaceutical Sciences, Andhra University, Visakhapatnam for providing facilities for a smooth run of this research work

 

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Received on 14.11.2024      Revised on 01.03.2025 Accepted on 12.04.2025      Published on 06.05.2025 Available online from May 10, 2025 Asian Journal of Pharmaceutical Analysis. 2025; 15(2):109-115. DOI: 10.52711/2231-5675.2025.00018 ©Asian Pharma Press All Right Reserved
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