INTRODUCTION:
Chemically known as (E)-1-(diphenylmethyl)-4-3-phenyl (prop-2-enyl) piperazine, cinnarizine (CIN) is a piperazine derivative with calcium channel and histamine H1-receptor inhibiting action. It is utilised to treat the symptoms of nausea and dizziness brought on by Meniere disease and other vestibular diseases. Additionally, it is employed in the therapy of a number of peripheral and vascular illnesses as well as the prevention and treatment of motion sickness. depicts the Cinnarizine's structural makeup in Figure 1.1-2
Domperidone Maleate (DOM) is chemically 5-chloro-1-[l-[3-(2, 3-dihydro- 2-oxo-1H- benzimidazol-l -yl) propyl]-4-piperidinyl] - l, 3-dihydro-2H-benzimidazol-2-one maleate.
It is an anti-emetic dopamine-receptor antagonist drug that does not penetrate the blood brain barrier but does access the chemoreceptor trigger zone, to be used to prevent the nausea. It is used to treat vomiting due to cytotoxic therapy as well as gastrointestinal symptoms. The structure of Domperidone Maleate is shown in Figure 1.1-2
(A)
(B)
Figure 1: (a) Cinnarizine (b) Domperidone maleate
The goal of stability and related substance studies is to provide evidence regarding how a drug substance's or product's quality changes over time while being influenced by a number of environmental circumstances.3,4 Presence of impurities critically effect the stability and pharmacological action of pharmaceutical API and drug product.5-9 An essential study for vaccine Formulation Development.10 UV Spectrophotometric methods (simultaneous equation methods/vierodts) and LC MS-MS are widely acceptable for simultaneous estimation of pharmaceutical combinations.11,12 Analytical quality by design [AQbD] and CCD help in regulatory compliance For RP-HPLC method development, stress testing or stability indicating methods.13-21
Domperidone Maleate (DOM) and Cinnarizine (CIN) are both available as tablets that can be used to treat vertigo. Literature survey revealed that various analytical methods have been reported for estimation of individual drugs or in combination with other drugs including UV22-29 and HPLC30-42. From the above literature survey it was found that one stability indicating HPLC metho dis available for estimation of this combination, where % degradation found in all five conditions is almost similar, degradation chromatogram and peak purity data was not given which create ambiguity and also salt from of DOM is not used, which is available in market.43 The development of a stability-indicating RP-HPLC method for the simultaneous measurement of cinnarizine and domperidone maleate in tablet dosage form is therefore necessary and valuable.
MATERIAL AND METHOD:
Chemicals and Reagents:
Cinnarizine and Domperidone Maleate were obtained as free samples from Rakshit Drugs Pvt. Ltd. and Vaikunth Chemicals Pvt. Ltd, respectively. A local pharmacy sold STUGIL, a pharmaceutical tablet dosage form comprising 20mg of cinnarizine and 15mg of domperidone maleate. Water, acetonitrile, and methanol (HPLC grade, Finar) were employed. Potassium dihydrogen phosphate and orthophosphoric acid (Molychem, Mumbai).
Chromatographic Condition:
A Shimadzu HPLC instrument equipped with LC-solution software and Nucleosil C18, (25cm x 4.6mm, 5 µm) column was used. The mobile phase chosen was potassium dihydrogen phosphate (pH-3)(70:30%v/v). Flow rate was adjusted to 1ml/min and λmax was selected 271nm.
Preparation of Solution:
Buffer (10mM Potassium dihydrogen phosphate, pH-3)
0.68g of KH2PO4 was disslove in 500mL water adjusts pH-3 with OPA.
Mobile phase:
Mix Acetonitrile and 10mM Potassium Dihydrogen Phosphate pH-3 in the ratio of 70:30% v/v.
Diluents:
Acetonitrile was used as diluent.
Preparation of Standard stock solution:
Standard stock solution of 100μg/mL for CIN and 127.2 μg/mL for DOM were prepared by using acetonitrile as a diluent.
Preparation of working solution of mixture of Cinnarizine and Domperidone Maleate:
Working solution of 10μg/mL for CIN and 12.72μg/mL for DOM were prepared by appropriate dilution.
Preparation of Sample solution:
20 tablets were weighed and finely powdered. Transfer 86.8mg of sample in 100mL volumetric flask. About 70 % of diluent was added and sonicate for 20min and diluted up to mark with diluent (100μg/mL and 127.2 μg/mL for CIN and DOM respectively). Further dilute the above solution to obtain 10μg/mL and 12.72μg/mL for CIN and DOM respectively.
Forced Degradation Studies:
Acid hydrolysis was carried out using 0.1 N HCL for 1 hour and basic hydrolysis was carried out using 0.1N NaOH for 2hours and then mixture was neutralized and make up the volume up to the mark to attain final concentration. Oxidative degradation was carried out using 1ml of 3% H2O2 for 30min. Thermal degradation was carried out at 60şC for 6hours. Photolytic degradation carried out under UV light for 6hours.
Method Validation:
According to the ICH (Q2R1) guideline, the analytical validation parameters for this proposed method were established.
System suitability:
The system's applicability was tested using five replicate injections of conventional CIN and DOM solutions. The tailing factor, retention duration, and theoretical plates of a standard chromatogram were then examined in relation to the system appropriateness parameters.
Linearity:
The standard stock solution was properly diluted to achieve concentrations of 7.6–45.6 μg/mL of DOM and 8–48 μg/mL of CIN with diluent.
Specificity:
To test for excipient interference, specificity was done by injecting diluent, placebo, and sample solution.
LOD and LOQ:
Formulas were used to determine the limits of detection (LOD) and quantitation (LOQ). Standard deviation (SD) of the intercepts was computed after five repetitions of the calibration curve.
Accuracy:
Three distinct drug concentration levels 80, 100, and 120% of the desired concentrations were used to test the method's accuracy in triplicate. By spiking the above concentration to a placebo, the study was conducted. Calculating the % recovery allowed for an evaluation of the method's accuracy.
Precision:
Repeatability tests were conducted using 6 replicates at the CIN and DOM assay concentrations. Three different concentration levels (80, 100, and 120%) of CIN and DOM were tested in triplicate for intra- and inter-day variations. Results are expressed in the form of RSD.
Robustness:
By purposefully making minor adjustments to experimental parameters such flow rate, pH, and mobile phase composition, the robustness of the approach was established. The flow rate was adjusted by 0.1 (0.9, 1, and 1.1mL/min), the pH by one (2.9, 3, and 3.1), and the mobile phase composition by two percent (68:32% v/v, 70:30% v/v, and 72:28% v/v).
RESULTS AND DISCUSSION:
Method development and optimization of chromatographic conditions
Different buffer pH settings and various solvent concentrations, including methanol and acetonitrile, were employed to produce satisfactory separation. However, at a flow rate of 1 mL/min measured at a detection of 271 nm, Acetonitrile and phosphate buffer pH 3 in the ratio of 70:30% v/v generated good satisfactory results.
Figure 2: Chromatogram of optimized condition
SystemSuitability:
Six replicates of CIN and DOM working standards samples were injected to test the system's suitability. The parameters retention time (Rt), which was found to be 8.9mins and 4.4mins, tailing factor, which was found to be 1.7 and 1.5, and theoretical plate (N), which was found to be 5044 and 3451, respectively, were all studied.
Forced Degradation Study:
The range of the observed percentage of degradation was 10.97–17.80%. The peak purity of the medications that passed is displayed in Table 2 and Figure 3 because there was no interference from degradants.
(a)
(b)
(c)
(d)
(e)
Figure 3: Chromatogram of (a) acid hydrolysis degradation (b) base hydrolysis degradation (c) oxidative degradation (d) thermal degradation (e) photolytic degradation
Table: 1 Stability studies for domperidone maleate and cinnarizine
|
|
Domperidone Maleate |
Cinnarizine |
||
|
Stress conditions |
% Degradation |
Peak Purity Index |
% Degradation |
Peak Purity Index |
|
Acid (0.1 N HCl for 1 hr) |
11.18 |
0.99 |
15.13 |
0.98 |
|
Base (0.1 N NaOH for 2 hr) |
10.97 |
0.99 |
13.34 |
0.99 |
|
Oxidative (3% H2O2 for 30min) |
17.80 |
0.99 |
16.14 |
0.99 |
|
Thermal (60 ˚C for 6 hr) |
16.43 |
0.98 |
13.09 |
0.99 |
|
Photolytic (UV light for 6 hr) |
16.11 |
0.98 |
13.76 |
0.99 |
Method Validation:
According to the ICH (Q2R1) guideline, the described technique has been verified for linearity, accuracy, limit of detection, limit of quantification, precision, and robustness.
Specificity:
Excipient interference was less than 0.5% for both medications, therefore it is not noticeable at the working wavelength of 271nm. Method is hence Specific.
Linearity:
The process is sequential. The calibration curve for CIN and DOM was determined to be between 8 to 48μg/mL and 7.4 to 45.6μg/mL, respectively. For CIN and DOM, it was discovered that y = 15115x+114017, R2 = 0.9987, and y = 7788.8x+27305, R2 = 0.9981, respectively, are the regression equations and correlation coefficients.
Accuracy:
The method is accurate as %Recovery was found in the range of 99.53-100.47% for both the drugs, data are shown in Table 2.
Table: 2 Summary of accuracy
|
Accuracy |
||||
|
Parameter (n=3) |
Domperidone Maleate |
Cinnarizine |
||
|
|
Amount added (µg/mL) |
% Recovery |
Amount added (µg/mL) |
% Recovery |
|
80%level |
15.2 |
100.28 |
16 |
99.53 |
|
100% level |
19 |
99.88 |
20 |
100.12 |
|
120% level |
22.8 |
100.47 |
24 |
99.57 |
Precision:
RSD is a measure of repeatability and intermediate precision. As RSD was discovered to be 2%, the proposed approach is accurate. Table 3 provides a summary of the findings.
Table: 3 Summary of precision
|
Precision |
|||
|
Drugs |
Level |
Intra-day RSD |
Intra-day RSD |
|
DOM |
80% |
0.20 |
0.14 |
|
100% |
1.19 |
1.67 |
|
|
120% |
0.37 |
0.72 |
|
|
CIN |
80% |
0.21 |
0.20 |
|
100% |
0.02 |
0.21 |
|
|
120% |
0.26 |
0.07 |
|
Limit of Detection and Limit of Quantification:
For DOM and CIN, the LOD values were discovered to be 0.67μg/mL and 1.00μg/mL, respectively. For DOM and CIN, the LOQ values were discovered to be 2.02 μg/mL and 3.02μg/mL, respectively.
Robustness:
When the flow rate, pH, and mobile phase composition were purposefully changed, the RSD was determined to be less than 2, indicating that the approach is robust. Table 4 presents the outcomes.
Table: 4 Summary of robustness
|
Robustness |
|||
|
|
Domperidone Maleate |
Cinnarizine |
|
|
Parameter |
Change |
RSD |
RSD |
|
Flow Rate (mL/ min) |
0.9 |
1.03 |
0.97 |
|
1.0 |
1.33 |
1.30 |
|
|
1.1 |
1.54 |
1.15 |
|
|
pH |
2.9 |
1.17 |
1.05 |
|
3.0 |
0.97 |
1.17 |
|
|
3.1 |
1.31 |
1.28 |
|
|
Mobile Phase Composition Ratio |
68:32 |
1.05 |
1.49 |
|
70:30 |
0.85 |
1.01 |
|
|
72:28 |
1.30 |
1.46 |
|
Forced degradation study:
Even so, attenuated circumstances were used to obtain force depreciation in the range of 5-20%. In each case, this was accomplished. In an oxidative environment, CIN and DOM shown significant degradation. There is no additional peak visible in the improved chromatogram. The degradants could be clearly seen from the main peak. Peak purity index proved there was no peak merging.
Assay of tablet dosage form:
Percentage drug content of tablet dosage form of CIN and DOM was found between 99.18-99.63%. The data is given in Table 5. Thus method can be used for routine assay of tablet dosage form.
Table: 5 Assay of marketed formulation
|
Drug (n=3) |
Label Claim(mg) |
Amount Found(mg) |
% Assay |
|
DOM |
19 |
18.87 |
99.18 |
|
CIN |
20 |
19.95 |
99.63 |
CONCLUSION:
The present work describes a stability indicating RP-HPLC-PDA method for the detection of Cinnarizine and Domperidone Maleate in tablet dosage form, which was successfully validated. Validation was carried out for Cinnarizine and Domperidone Maleate as per ICH(Q2R1) guideline. By RP-HPLC, the accuracy of Cinnarizine and Domperidone Maleate was discovered in the range of 99.53-100.12 and 99.88-100.47 percent, and it was found that precision was less than 2 in terms of RSD, For and Domperidone Maleate and Cinnarizine, the LOD values Was found as 0.67μg/mL and 1.00 μg/mL, respectively. For and Domperidone Maleate and Cinnarizine, the LOQ values were discovered to be 2.02 μg/mL and 3.02μg/mL, respectively and robustness was less than 2 in terms of RSD.Conditions for degradation included acidic, basic, oxidative, thermal, and photolytic. The technique is sufficient to distinguish between the peaks of active pharmaceutical ingredients (API) and degradants (generated during stress condition). Thermal >Basic >Photolytic >Acidic > Oxidative and Basic >Acidic >Photolytic >Acid > Oxidative, respectively, are the order of stability for cinnarizine and domperidone maleate. The suggested stability indicating approach can therefore be used in pharmaceutical analysis for quality assurance and monitoring drug stability.
ACKNOWLEDGEMENT:
The Authors are thankful to B. K. Mody Government Pharmacy College, Rajkot, Gujarat, India for providing necessary facilities to carry out the research work. Special thanks to Rakshit drugs Pvt. Ltd. and Vainkuth Chemicals Pvt. Ltd. for providing drug.
REFERENCES:
1. Rang HP, Dale MM, Ritter RJ. Rang &Dales's Pharmacology. Elseveir Publication. 2012.
2. Indian Pharmacopoeia 7th edn., Government of India Ministry of Health & Family Welfare, Indian Pharmacopoeial Commission, Ghaziabad, 2014, Vol. II, pp. 1397-1398, 1613-1614.
3. Vyas AJ, Rathod N, Patel AI, Prajapati R, Patel NK, Patel AB. Analytical Method Development And Validation Of Stability Indicating Method And Related Substance By Using RP-HPLC Of Drug Substance. Pharma Science Monitor. 2017; 8(2): 409-419.
4. Vyas AJ, Taviyad M, Patel NK, Chotaliya UJ, Singh S, Patel AB, Patel AI. Chromatographic Method Development And Validation For Related Substance. Pharma Science Monitor. 2017; 8(2): 32-39.
5. Patel AI, Prajapati KB, Vyas AJ, Patel AB, Patel NK, et al. Determination and validation of phthalate impurities in milk by UV-spectrophotometry method. Pharma Science Monitor. 2021; 10(4): 49-58.
6. Vyas AJ, Rajput M, Patel NK, Chotaliya UJ, Patel AB, Patel AI. Determination of genotoxic Impurity By Chromatographic Method. An International Journal Of Pharmaceutical Sciences. 2017; 8(2): 24-31.
7. Vyas AJ, Godhaniya JP, Patel AI, Patel AB, Patel NK, Chudasama A, Shah SR, et al. A review on carcinogenic impurities found in marketed drugs and strategies for its determination by analytical methods. Asian Journal of Pharmaceutical Analysis. 2021; 11(2): 159-169.
8. Patel AB, Asnani AH, Vyas AJ, Patel NK, Patel AI, et al. A brief review on genotoxic impurities in pharmaceuticals. Asian Journal of Pharmaceutical Research. 2021; 11(3): 187-193. doi: 10.52711/2231- 5691.2021.00034
9. Patel AB, Bundheliya AR, Vyas AJ, Patel NK, Patel AI, et al. A Review on Metal Impurities in Pharmaceutical. Asian Journal of Pharmaceutical Analysis. 2021; 11(3): 212-222. doi:10.52711/2231- 5675.2021.00038
10. Vyas AJ, Jha SA, Patel AB, Patel AI, Shah SR, et al. Review on simultaneous equation method (Vierodt's method). Asian Journal of Pharmaceutical Analysis. 2022; 12(2): 149-156. ;doi: 10.52711/2231-5675.2022.00026
11. Patel AI, Ram K, Guttikar S, Vyas AJ, Patel AB, Patel NK, Trivedi V. Rapid, sensitive and simple LC-MS/MS method development and validation for estimation of phenytoin in human plasma by using deuterated internal standard. Research Journal of Pharmacy and Technology. 2021; 14(6): 2937-2944. doi: 10.52711/0974-360X.2021.00515.
12. Vaghela A, Patel AB, Patel AI, Vyas AJ, Patel NK. Sample Preparation In Bioanalysis: A Review. International Journal Of Scientific & Technology Research. 2016; 5(5): 6-10.
13. Patel AI, Prajapati AB, Jolapara SH, Vyas AJ, Patel AB, Patel NK, Pandey MM. RP-HPLC method for determination of gemfibrozil using central composite design (CCD). Research Journal of Pharmacy and Technology. 2021; 14(6): 3009-3014. ;doi: 10.52711/0974-360X.2021.00527
14. Vyas AJ, Gol DA, Patel AI, Patel AB, Patel NK, Chavda JR, Lumbhani A, Chudasama A. Implementing Analytical Quality by Design (AQbD) Approach for Simultaneous Estimation of Tadalafil and Macitentan by RP-HPLC Method. Analytical Chemistry Letters. 2021; 11(4): 539-552. doi:10.1080/22297928.2021.1938215.
15. Vyas AJ, Visana NM, Patel AI, Patel AB, Patel NK, et al. Analytical Quality by Design in Stress Testing or Stability - Indicating Method. Asian Journal of Pharmaceutical Analysis. 2021; 11(2): 170-178. doi: 10.52711/2231-5675.2022.00023
16. Vyas AJ, Patel SM, Patel AB, Patel AI, Patel NK, et al. Stability testing: An Essential study for Vaccine Formulation Development.Asian Journal of Pharmaceutical Analysis. 2022; 12(1): 29-6. doi: 10.52711/2231-5691.2022.00006
17. Kothapalli LP, Shahane RR, Nanda RK, Thomas AB. Development and validation of stability indicating HPTLC method for simultaneous estimation of Domperidone maleate and Naproxen sodium in pharmaceutical formulations. Asian J. Research Chem. 2016; 9(7): 350-356. DOI: 10.5958/0974-4150.2016.00053.5
18. Jogdand S, Mane K, Jadhav R, Dyade GK. AQBD Approach in Chemo metric assisted Method Development for the Estimation of Ciprofloxacin and Metronidazole by UV-VIS Spectrophotometry. Asian Journal of Pharmaceutical Research. 2022; 12(3): 183-1. DOI: 10.52711/2231-5691.2022.00030
19. Buralla KK, Parthasarathy V. Central Composite Design based Development and Validation of an RP-HPLC Method for Paclitaxel in Bulk and Pharmaceutical Dosage Form. Research J. Pharm. and Tech. 2020; 13(10): 4895-4902. DOI: 10.5958/0974-360X.2020.00861.6
20. Utharalakshmi N, Kumar AG, Narendrakumar G. Optimization of Cellulase Producing Aspergillus flavus SB4 by Solid State Fermentation using Response Surface Methodology (RSM)-CCD. Research J. Pharm. and Tech. 2015; 8(4): 349-354. DOI: 10.5958/0974-360X.2015.00058.X
21. Sumalatha B, Babu DJ, Venkatanarayana A, Reddy PR, Sruthi PD. Experimental Investigation on Biosorption of Chromium from Aqueous Solution using Citrus limonium peel: Optimization of Process Parameters using Central Composite Design. Research J. Pharm. and Tech 2018; 11(12): 5253-5264. DOI: 10.5958/0974-360X.2018.00958.7
22. Abdelrahman MM. Simultaneous determination of Cinnarizine and Domperidone by area under curve and dual wavelength spectrophotometric methods. Spectrochim Act – Part A Mol Biomolecular Spectroscopy. 2013; 113: 291-96. DOI: 10.1016/j.saa.2013.04.120.
23. Shedpure PS, Patel PA, Sawant SD, Dole MN. Spectrophotometeric Determination of Dexrabeprazole Sodium and Domperidone Maleate in Bulk and Capsule Dosage Form by First Order Derivative Spectroscopy. Research J. Pharm. and Tech. 2011; 4(7): 1086-1089.
24. Ahmed R, Supriya RS, Darade RS. Spectrophotometric Method for Simultaneous Estimation of Paracetamol and Cinnarizine in Tablet Dosage Forms. Research J. Pharm. and Tech. 2012; 5(5): 667-671.
25. Tarkase KN, Tarkase MK, Dhokhe MD. Development and validation of Spectrophotometric Method for Simultaneous Estimation of Cinnarizine and Domperidone Maleate in Pure and Tablet Dosage Form. Int. J Pharmaceu Sci and Res. 2012; 3. DOI: http://dx.doi.org/10.13040/IJPSR.0975-8232.3(8).2700-04.
26. Maissa YS, Eman SZ, Tarass MF. Simultaneous determination of domperidone and cinnarizine in a binary mixture using derivative spectrophotometry, partail least squares and principle component regression calibration. J Pharmaceu and Biomed Ana. 2003; 375: 211-6.
27. Abdine H, Belal F, Zoman N. Simple spectrophotometric determination of cinnarizine in its dosage forms. IL Farmaco. 2005; 57: 267-71. DOI: 10.1016/S0014-827X(02)01204-1.
28. Chauhan S, Kumar P, Kothiyal, P. Validated Method Development for the Estimation of Domperidone by UV-Spectroscpy. Int J Pharma Res & Review. 2005; 4: 1-7.
29. Kalyankar TM, Wadher SJ, Kulkarni PD, Panchakshari PP. Simultaneous Estimation and Development of UV Spectroscopic Method for Determination of Cinnarizine and Domperidone in Bulk and Pharmaceutical Formulation. International Journal of PharmTech Research. 2014; 6(1): 323-329.
30. Naga SM, Kumari SA. Validated RP-HPLC Method for simultaneous Estimation of Cinnarizine and Domperidone in Bulk and Pharmaceutical Dosage Form. J Pharmaceu Sci and Innovation. 2013; 2: 46-50.
31. Argekar AP, Shah SJ. Simultaneous determination of cinnarizine and domperidone maleate from tablet dosage form by reverse phase ion pair high performance liquid chromatography. J Pharmaceu and Biomed Ana. 1991; 19: 813-817. DOI: 10.1016/s0731-7085(98)00103-4.
32. Hanna NK, Rakowska M. High Performance Liquid Chromatographic Assay for Cinnarizine in Human Plasma. Acta Poloniac Pharmaceutica- Drug Research. 2007; 63: 407-11.
33. Navaneethan G, Karunakaran K, Elango KP. Stability indicating and simultaneous determination of Cinnarizine and Piracetam from capsule dosage form reverse phase high performance liquid chromatography. Indian J Chem Techno. 2013; 20: 323-326.
34. Santhosa B, Ravindranath A. Stability indicating RP-HPLC method for simultaneous estimation of Domperidone and Lafutidine in bulk and pharmaceutical dosage form. International J Pharma AndPharmaceu Sci. 2012; 4: 589-594.
35. Rajendraprasad Y, Rajasekhar KK, Shankarnanth V. RP-HPLC Method for the Estimation of Domperidone in Bulk and Pharmaceutical Formulations. Asin J Res Chem. 2009;2: 561- 64.
36. Sharma S, Sharma AK, Singh O. RP-HPLC Method Development and Validation of Domperidone in Solid Dosage Form. The Pharma Innovation. 2012; 1: 16-20.
37. Mahrouse MA, Zaher AA, Ghani AM. Validated Chromatographic Methods for Simultaneous Estimation of Cinnarizine in Binary Mixture with Domperidone and Paracetamol in Tablets. Current Pharmaceutical Analysis. 2019; 15. DOI: 10.2174/1573412914666180307154921.
38. Ravi P, Pravallika KE, Yashaswini M. Stability indicating RP-HPLC Method for Simultaneous Estimation of Domperidone and Cinnarizine in Bulk and pharmaceutical Dosage Form. Int J Pharm Sci Rev. 2017; 47: 45-52.
39. Kalyankar TM, Kulkarni PD, Panchakshari PP, Narute AS. Simultaneous RP-HPLC estimation of Cinnarizine and Domperidone in Tablet. Research J. Pharm. and Tech. 2014; 7(6): 650-654. DOI: 10.5958/0974-360X.
40. Moon SA, Korhale RV, Jadhav SL, Biradar NS, Puri DC, Shrikant A, Patil K. Development and Validation of RP-HPLC Method for Simultaneous Estimation of Lafutidine and Domperidone Maleate in Tablet Dosage Form. Asian J. Research Chem. 2012; 5(6): 781-786.
41. Akhtar J, Srivastava B, Sukla SS, Chaturvedi R, Baghel US. Simultaneous Estimation of Rabeprazole Sodium and Domperidone Maleate in Bulk and Tablet Dosage Form by Reverse Phase High Performance Liquid Chromatography. Research J. Pharm. and Tech. 2010; 3(1): 231-233.
42. Kalyankar TM, Kulkarni PD, Panchakshari PP, Narute AS. Simultaneous RP-HPLC estimation of Cinnarizine and Domperidone in Tablet. Research J. Pharm. and Tech. 2014; 7(6): 650-654.
43. Bayyari MA, Lara FT. Liquid Chromatography Tandem Mass Spectrometry Method for Determination of Domperidone in Human Plasma. J. Chem. Pharmaceu. Res. 2015; 7(1): 980-85.
Received on 26.09.2022 Modified on 30.11.2022
Accepted on 21.12.2022 © RJPT All right reserved
Research J. Pharm. and Tech 2023; 16(11):5225-5230.
DOI: 10.52711/0974-360X.2023.00847