DETERMINATION OF ELEMENTAL IMPURITIES IN ESLICARBAZEPINE ACETATE A PARTIAL SEIZURE DRUG BY USING ICP-MS

DETERMINATION OF ELEMENTAL IMPURITIES IN ESLICARBAZEPINE ACETATE A PARTIAL SEIZURE DRUG BY USING ICP-MS

Satish Ganta, T. Siva Rao *, Rama K. Srinivas, Suman Pallapati, Sridhar Bonam and G. Divya

Aurobindo Pharma Limited, Andhra University, Visakhapatnam, Andhra Pradesh, India.

ABSTRACT: Eslicarbazepine acetate is a chemical compound that has found medical use as a partial seizure drug. Monitoring of heavy metals (As, Mn, Cd, Cr, V, Mo, Cu, and Sb) in-process, intermediates, and final drug substances is an important activity in the pharmaceutical industry because of the potential for toxicity and the risk of serious health hazards even at very low doses. This research article established and validated an easy and rapid analytical method for determining eight heavy metals in Eslicarbazepine acetate. Drugs must first be processed through acid digestion using microwave radiation before being analyzed for these elemental impurities. The % RSD of the LOQ solution was found to be < 20.0 for all the elements. The analytical method seems linear, with a correlation coefficient > 0.99. Eslicarbazepine acetate sample amounts spiked at three different concentrations, resulting in acceptable percentage recoveries of heavy metal ions ranging from 70% to 150%. Individually, precision and robustness for all conditions met the acceptable limits. Heavy metal analysis by ICP-MS is a powerful technique; therefore, the present method is selective, sensitive, accurate, linear, precise, and robust. It can also be used for routine quantitatively determining eight elemental impurities in Eslicarbazepine acetate.

Keywords: Eslicarbazepine Acetate (ESA), ICP-MS, Heavy metals, Genotoxic Impurities

INTRODUCTION: Eslicarbazepine Prodrug to Eslicarbazepine being acetate (ESA) is likewise an oxcarbazepine active metabolite. (S)-10-acetoxy-10, 11-dihydro-5H-dibenz [b,f] azepine5-carboxamide is its chemical name Fig. 1. Due to structure change, it is shown to increase effectiveness and safety and to prevent the generation of a harmful epoxide metabolite. It can be employed to treat trigeminal neuralgia and bipolar disorder.

Eslicarbazepine Acetate was administered to patients who had partial-onset seizures that are resistant to testing, and it was discovered to be effective and well-tolerated ^1-5. The introduction of different metal contaminants into drug products, bulk drug compounds, and their intermediates, including using electrodes, reaction containers, and other synthesis-related equipment, can occur in several ways.

Most notably, metals can be added by using catalysts at various stages of the manufacture of various drugs. Concepts of monitoring and accurate assessments of concentrations for toxic and hazardous elements are required to develop risk assessment and sustainable development. Very few methods become available in the literature such as FT-IR ⁶, HPLC ^7-11, HPTLC ¹², LC-MS/MS ¹³, for the assessment of ESA and their related organic impurities. Possibly harmful substances have ill effects on the human body. These may be mainly monitored to reduce uncontrolled anthropogenic activities and protect public health ^14-15. To quantify these heavy metal ions for this study, sensitive and precise analytical techniques must be employed. Among the modern analytical spectral techniques, ICP-MS was found to be selective, sensitive, and rapid for determining these genotoxicimpurities. A microwave oven is a commonly used technique in the pharmaceutical industry for liberating heavy metal ions from organic matrices, which has good repeatability and the least loss of target elements. According to published reports for the determination of heavy metals, very few of trace elements related methods by ICP-MS were available, which are in plants ¹⁶, cereals ¹⁷, breast milk ¹⁸, dietary supplements ¹⁹, solid waste ²⁰, rice ²¹, etc ^22-34.

No ICP-MSmethod was applied for the assessment of heavy metal ions like Cadmium (Cd), Arsenic (As), Chromium (Cr), Vanadium (V), Molybdenum (Mo), Manganese (Mn), Copper (Cu) and antimony (Sb) in Eslicarbazepine Acetate. At present, our research study aims to develop an ICP-MS method for the quantification of genotoxic heavy metal ions in Eslicarbazepine acetate and validate the method.

FIG. 1: STRUCTURE OF ESA

EXPERIMENTAL: ICP-MS instrumentation setup for elemental impurity determination: Heavy metal ion determination in this study was accomplished by employing an Agilent 7800 Tandem ICP-MS (ICP-MS/MS, make: Agilent Technologies from Japan) equipped with nickel cones. Table 1 summarizes the tuning settings and operating parameters for detecting eight elemental impurities in Eslicarbazepine acetate.

TABLE 1: ICP-MS INSTRUMENT OPERATING CONDITIONS AND PARAMETERS

Samples and Reagents used for ICP-MS/MS analysis: ICP-MS/MS analysis was executed by employing trace metal grade concentrated Nitric acid (HNO₃ :Fluka), Cadmium (Cd), Arsenic (As), Chromium (Cr), Vanadium (V), Molybdenum (Mo), Manganese (Mn), Copper (Cu) and antimony (Sb), as well as Tuning Solution (Agilent), Water (Milli-Q) and Hydrogen Peroxide (Merck AR grade). All solution preparations were carried out in a fume hood. Chemicals, reagents, and standards of their grades are summarized in Table 2.

TABLE 2: CHEMICALS, REAGENTS AND STANDARD

Nitric acid is utilized as a blank reagent solution as well as a washing/rinsing solution for an ICP-MS measurement since it has the simplest spectra of all the acids and the lowest background levels when compared to pure water. The sensitive measurement of metals at ppb (1 ppb = 10^-9 g ml^-1) or ppt (1ppt = 10^-12 g ml^-1) levels in sample solutions generally necessitate a high-purity reagent. As a result, selecting an appropriate nitric acid grade (ICP grade, make: Fluka, Batch No. J2120) was critical for the elemental analysis.

Preparation of Solutions: Diluent preparation (2% v/v HNO3): Conc. nitric acid (20 mL) should be added to 200 milliliters of demineralized water in a 1.0 L volumetric flask to make up the remaining volume.

Making Standard Stock Solutions:

Preparation of Standard Stock Solutions -A: Transfer 0.25 mL of Cd standard solutions at 1000 ppm into volumetric flasks or 10 mL polypropylene tubes, then add diluent to produce the volume.

Preparation of Standard Stock Solution-B: Transfer 10 mL polypropylene tubes or volumetric flasks with the following contents:

1.0 mL of above standard stock solution-A, 0.075 mL of As, and 0.5 mL of V of 1000 ppm standard solution. Fill the remaining space with diluent.

Preparation of Standard Stock Solution-C: In 10 mL polypropylene tubes or volumetric flasks, transfer 1.0 mL of the aforementioned stock solution-B, 0.6 mL of the Sb and 0.75 mL of the Mn from the 1000 ppm standard solution. Fill the remaining space with diluent.

Transfer 1.0 mL of above standard stock solution-C, 0.15 mL of Mo, 0.15 mL of Cu, and 0.55 mL of Cr into 10 mL polypropylene tubes or volumetric flasks, and then dilute to the required volume.

Making the internal standard solution (10 ppm) of scandium, yttrium, germanium and indium: Transfer 0.5 ml of a standard solution containing 1000 ppm of scandium, yttrium, germanium and indium into a 50 ml volumetric flask or polypropylene tube, dilute to the proper level and aspirate into an ICP-MS.

RESULTS AND DISCUSSIONS: To validate the analytical procedures for the quantitative determination of the heavy metals Cadmium, Arsenic, Vanadium, Chromium, Manganese, Molybdenum, Copper, and Antimony in Eslicarbazepine Acetate, the following factors have been considered and assessed: applicability, specificity, range, linearity, the minimum detection limit, repeatability, the limit of quantification, accuracy, and robustness.

Specificity: The capacity of a method to test an analyte specifically or selectively in the presence of components (such as Eslicarbazepine Acetate, Cd, As, V, Cr, Mn, Mo, Cu and Sb) that may be anticipated to be present in the sample is known as specificity. Specificity was confirmed by examining the interference in the ICP-MS with the blank and standard solutions. Since there was less than 3.0% detected interference between the test blank and the blank, the approach is specific.

Limits of Quantitation (LOQ) and Detection (LOD): The lowest concentration or amount of an analyte (Cd, As, V, Cr, Mn, Mo, Cu and Sb) that can be measured with a tolerable degree of statistical certainty is known as the minimum detection limit. The limit of quantification, or LOQ, is the lowest concentration of the analyte that can be identified with a respectable level of accuracy, precision, and repeatability. To establish the LOQ value, predict the first calibration standard as (i.e., 25% specification level) LOQ and establish the LOD value as two times lower than LOQ value. For the establishment of LOD and LOQ values by employing of the new analytical approach of ICP-MS, analyze blank solution, LOD solution, and six injections of LOQ solution (i.e., 25% specification level) in ICP-MS. According to test concentration, the LOD and LOQ for the element were determined to be 0.06 ppm and 0.13ppm for Cadmium (Cd), 0.11 ppm and 0.38 ppm for Arsenic (As), 1.25ppm and 2.5 ppm for Vanadium (V), 83.33 ppm and 275 ppm for Chromium (Cr), 11.36 ppm and 37.5 ppm for Manganese (Mn), 22.73 ppm and 75 ppm for Molybdenum (Mo), 22.7 ppm and 75.2 ppm for Copper (Cu) and 15ppm and 30ppmfor Antimony (Sb) Table 3.

TABLE 3: LOD AND LOQ DETERMINATION

Precision at the LOQ: The LOQ precisions were assessed using six replicates of the LOQ concentration to calculate the % RSD. The obtained %RSD of the element was 1.30% for Cadmium (Cd), 1.36% for Arsenic (As), 0.60% for Vanadium (V), 0.62% for Chromium (Cr), 0.45% for Manganese (Mn), 0.73 % for Molybdenum (Mo), 0.18% for Copper (Cu) and 1.31% for Antimony (Sb) Table 4.

TABLE 4: PRECISION AT LIMIT OF QUANTITATION

Linearity and Range: Calibration solutions were used to determine the calibration curves, y = ax + b. (y is the signal intensity, and x is the know concentration of the given analyte in the calibration solution). Five specified varied concentrations of each element standard were run under optimal working conditions, CPS was recorded, and a calibration curve was plotted spanning the range from LOQ to 200% to assess the linearity of the ICP-MS method. The squared correlation coefficient was found to be 1.00 for Cadmium (Cd), 1.00 for Arsenic (As), 1.00 for Vanadium(V), 1.00 for Chromium (Cr), 1.00 for Manganese (Mn), 1.00 for Molybdenum (Mo),1.00 for Copper(Co) and 1.00 for Antimony (Sb). The correlation coefficients for each element (Cd, As, V, Cr, Mn, Mo, Cu and Sb) in Eslicarbazepine Acetate were R ≥0.99 and therefore met the requirement. These results demonstrated the linearity of this ICP-MS method over the specified range of Eslicarbazepine Acetate; their corresponding results are given in Table 5 to Table 12, and graphs are depicted Fig. 2 to Fig. 9.

TABLE 5: LINEARITY RESULTS OF CADMIUM IN ESA

TABLE 6: LINEARITY RESULTS AND GRAPH OF ARSENIC IN ESA

TABLE 7: LINEARITY RESULTS AND GRAPH OF VANADIUM IN ESA

TABLE 8: LINEARITY RESULTS AND GRAPH OF CHROMIUM IN ESA

TABLE 9: LINEARITY RESULTS AND GRAPH OF MANGANESE IN ESA

TABLE 10: LINEARITY RESULT AND GRAPH OF MOLYBDENUM IN ESA

TABLE 11: LINEARITY RESULTS AND GRAPH OF COPPER IN ESA

TABLE 12: LINEARITY RESULTS AND GRAPH OF ANTIMONY IN ESA

FIG. 2: LINEARITY GRAPH FOR CADMIUM IN ESA

FIG. 3: LINEARITY GRAPH FOR ARSENIC IN ESA

FIG. 4: LINEARITY GRAPH FOR VANADIUM IN ESA

FIG. 5: LINEARITY GRAPH FOR CHROMIUM IN ESA

FIG. 6: LINEARITY GRAPH FOR MANGANESE IN ESA

FIG. 7: LINEARITY GRAPH FOR MOLYBDENUM IN ESA

FIG. 8: LINEARITY GRAPH FOR COPPER IN ESA

FIG. 9: LINEARITY GRAPH FOR ANTIMONY IN ESA

Precision: To assess the precision, the %RSD was calculated. To determine the analytical instrument system precision or whether the instrument can consistently reproduce the measurement, the aspirated diluent, the system's precision solution, the calibration standards, the calibration blank, and the standard check solution. Calculate the RSD percentage as well as the variance percentage for six replicate aspirations. Software is utilized to determine the calibration curve's correlation coefficient. For each element Cd, As, V, Cr, Mn, Mo, Co, and Sb, the percentage RSD for 6 replicates of the system precision should not be greater than 15.0. The precision results are represented in Table 13.

TABLE 13: PRECISION RESULTS OF EACH ELEMENT IN ESLICARBAZEPINE ACETATE

Accuracy/ Recovery Study: The study on the accuracy of the method used to be decided by doping the respective concentration solution of element in test preparation and determining the content of 8 elemental impurities from test preparation. This can be expressed as percentage recovery R [%]. Accuracy was obtained by reading the pure sample and three known concentrations (LOQ, 50%, 100% and 150 %) of samples. The accuracy of the method is determined by spiking the sample with Cd, As, V, Cr, Mn, Mo, Cu and Sb in Eslicarbazepine Acetate elements at LOQ, 50%, 100% and 150% of the specification level concentration as well as recovery studies were carried out. We evaluated the % Rec obtained; the results were within the range of 95.5% to 102.7% for Cadmium, 96.8% to 106% for Arsenic, 95.5% to 104.5% for Chromium, 96.2% to 105.5% for Vanadium, 97% to 107.9% for Manganese, 95.3% to 104.5% for Molybdenum, 98.5% to 103.8% for Copper, 98.9% to 100.4% for Antimony. The obtained % recovery was well within the limit of 70% to 150%, and accuracy results were presented in Table 14.

TABLE 14: ACCURACY / RECOVERY STUDY OF EACH ELEMENT IN ESLICARBAZEPINE ACETATE

Robustness Study: The robustness study of these elements (Cd, As, V, Cr, Mn, Mo, Cu and Sb) in Eslicarbazepine Acetate was administered by varying the instrument parameter of ICP-MS and discovered the content material of heavy metals. By proving the analytical method's reliability in the event of anticipated changes in volume: %, its robustness will be established. Each analyte's recovery value should range from 70.0% to 150%. Integration time changes: % RSD cannot exceed 15.0% for every given condition. As the recovery results obtained from the study were within the acceptable limit of recovery Cadmium, Arsenic, Vanadium, Chromium, Manganese, Molybdenum, Copper, and Antimony for preparations of Sample Spiked with 100% Levels of which were well within the acceptance criteria. The % RSD for Arsenic (As), Cadmium (Cd), Chromium (Cr), Vanadium (V), Molybdenum (Mo), Manganese (Mn), Copper (Cu), and Antimony (Sb), for six injections of solutions at 25% (+10% and -10%) level which were well within the acceptance criteria. Table 15 and Table 16 display the element's obtained results.

TABLE 15: ROBUSTNESS STUDY RESULTS (CHANGE IN VOLUMES +10%)

TABLE 16: ROBUSTNESS STUDY RESULTS (CHANGE IN INTEGRATION TIME + 10%)

CONCLUSION: An ICP-MS method has been developed for the selective, sensitive, linear, precise, robust, and accurate determination of Cadmium (Cd), Arsenic (As), Manganese (Mn), Vanadium (V), Molybdenum (Mo), Chromium (Cr), Copper (Cu) and Antimony (Sb) in Eslicarbazepine acetate.

This method produced high precision (%RSD less than 15.0 for each element), accuracy (% average recovery of each element at each level lay between 70% and 150%), linearity (r² result was more than 0.99 for all the elements), LOD (the LOD response was higher than the blank response for all the elements), and LOQ (the % RSD of the analyte response for six replicates of the LOQ solution was less than 20.0 for all the elements). The samples were prepared using a simple digestion method; however, no matrix interferences were found. Considering what the sample analysis revealed, it can be concluded that Eslicarbazepine acetate complies with the regulations on the maximum residue limits established by the various regulatory agencies because these harmful metals are well below the permitted limit.

ACKNOWLEDGMENT: The authors are thankful to the Professor. T. Siva Rao from Andhra University for providing the necessary facilities to carry out the present research work.

CONFLICTS OF INTEREST: No conflict of interest from the authors.

REFERENCES:

1. Singh A and Trevick S: The Epidemiology of Global Epilepsy. Neurol Clin 2016; (34): 837-847.
2. Alves G, Figueiredo I, Castel-Branco M, Loureiro A, Fortuna A, Falcao A and Caramona M: Enantioselective HPLC-UV method for determination of eslicarbazepine acetate (BIA 2-093) and its metabolites in human plasma. Biomed. Chromatogr 2007; (21): 1127-1134.
3. Alves G, Fortuna A, Sousa J, Direito R, Almeida A, Rocha M, Falcao A and Soares-da-Silva P: Enantioselective Assay for Therapeutic Drug Monitoring of Eslicarbazepine Acetate: No Interference with Carbamazepine and Its Metabolites. Ther Drug Monit 2010; (32): 512-516.
4. Almeidaand L and Soares-da-Silva P: Eslicarbazepine acetate (BIA 2-093). Neurotherapeutics 2007; (4): 88-96.
5. Fortuna, Sousa J, Alves G, Falcaoand P and Soares-da-Silva A: Development and validation of an HPLC-UV method for the simultaneous quantification of carbamazepine, oxcarbazepine, Eslicarbazepine acetate and their main metabolites in human plasma. Anal Bioanal Chem 2010; (397): 1605-1615.
6. Ravi Prasad Pandit, Bhuvaneswari Kotamarthi, Rajani Kompally and Anu Radha: FT-IR Spectroscopic Assay Method for Eslicarbazepine Acetate in Bulk and Tablet Formulations. International Journal of Pharmaceutical Chemistry 2015; (05): 255-259.
7. Sanjeeva Reddy Kallam, Srikanth J and Prakash KV: Development and Validation of an Inductively Coupled Plasma Mass Spectrometry (ICP-MS) Method for the Determination of 17 Trace Metals in Ingenol Mebutate (API). IOSR J of Pharma and Biolog Sci 2016; (11): 6-11.
8. Saji Thomasa, Amber Bhartia, Pawan Kumar Maddhesiaa, Sanjeev Shandilyaa, Ashutosh Agarwala, Dharamvirb, Sujay Biswasb, Vikas Bhansalb, Ashish Kumar Guptab, Praveen Kumar Tewarib and Chandra S. Mathelac: Highly efficient, selective, sensitive and stability indicating RP-HPLC–UV method for the quantitative determination of potential impurities and characterization of four novel impurities in Eslicarbazepine acetate active pharmaceutical ingredient by LC/ESI-IT/MS/MS. J of Pharmaceutical and Biomedical Analysis 2012; (61): 165-175.
9. Moneand MK and Chandrasekhar KB: Development of liquid chromatographic enantiomer separation methods and validation for the estimation of (R)-enantiomer in Eslicarbazepineacetate. J Pharm Biomed Anal 2011; (54): 248-251.
10. Singh M, Kumar L, Arora P, Mathur SC, Saini PK, Singh RM and Singh GN: Development and Validation of an RP-HPLC Method for Quantitative Estimation of Eslicarbazepine Acetate in Bulk Drug and Tablets. Indian J Pharm Sci 2013; 75: 736-739.
11. Mudigonda Srinivas, Narasimha Rao Avupati and Shakil Saitand K. Mukkanti: Stability indicating HPLC method for the determination of Eslicarbazepine acetate and its impurities in bulk drugs and pharmaceutical dosage forms. Journal of Liquid Chromatography & Related Technologies 2012; (35): 1550-1564.
12. Nikita V. Mali and Deepali A. Bansode: Stability indicating thin-layer chromatographic determination of Eslicarbazepine acetate as bulk drug: Application to forced degradation study. Der Pharmacia Lettre 2016; (8): 38-47.
13. Loureiro AI, Fernandes-Lopes C, Wright LC and Soares-da-Silva P: Development and validation of an enantioselective liquid-chromatography/tandem mass spectrometry method for the separation and quantification of Eslicarbazepine acetate, Eslicarbazepine, R-licarbazepine and oxcarbazepine in human plasma. Journal of Chromatography 2011; (879): 2611-2618.
14. McKelvey W, Charon Gwynn R, Jeffery N, Kass D, Thorpe LE, Garg RK, Palmer CD and Parsons PJ: A Biomonitoring Study of Lead, Cadmium and Mercury in the Blood of New York City Adults. Environ Health Perspect 2007; (115): 1435-1441.
15. Mumtaz MM, Ruiz P and De Rosa CT: Toxicity assessment of unintentional exposure to multiple chemicals. Toxicol Appl Pharmacol 2007; 223: 104-113.
16. Shchukin VM, Zhigilei ES, Erina AA, Yu. N Shvetsova, Kuz’mina NE and Luttseva AI: Validationof an ICP-MS method for the determination of mercury, lead, cadmium, and Arsenic in medicinal plants and related drug preparations. Pharma Chemistry J 2020; (54): 968-976.
17. Sung Hwa Choi, JiYeon Kim, EunMi Choi, Min Young Lee, JiYeon Yang, Gae Ho Lee, Kyong Su Kim, Jung-Seok Yang, Richard E. Russo, Jong Hyun Yoo, Gil-Jin Kang and Kyung Su Park: Heavy Metal Determination by Inductively Coupled Plasma – Mass Spectrometry (ICP-MS) and Direct Mercury Analysis (DMA) and Arsenic Mapping by Femtosecond (fs) – Laser Ablation (LA) ICP-MS in Cereals. Analytical Letters 2019; (52): 1-13.
18. Mariann Ecsedi-Angyal, Enikő Tatár, Mihály Óvári, Krisztina Kurin-Csörgei, GyulaZáray and Victor G. Mihucz: Determination of low-level Arsenic, lead, cadmium and mercury concentration in breast milk of Hungarian women. International Journal of Environmental Analytical Chemistry 2020; (100): 1-18.
19. Fernanda Costa Pinheiro MS, Diego Victor Babos, Ariane Isis Barros, Edenir Rodrigues Pereira-Filho and Joaquim Araújo Nóbrega: Microwave-assisted digestion using dilute nitric acid solution and investigation of calibration strategies for determination of As, Cd, Hg and Pb in dietary supplements using ICP-MS. J of Pharmaceutical and Biomedical Analysis 2019; (174): 471-478.
20. Wang Zhao: Determination of Six Heavy Metal Elements Such as Coin Solid Waste by ICP-MS. Earth and Environmental Science 2019; (300): 1-7.
21. Lidiane Raquel Verola Mataveli, Márcia Liane Buzzo, Luciana Juncioni de Arauz, Maria de Fátima Henriques Carvalho, Edna Emy Kumagai Arakaki, Richard Matsuzaki and Paulo Tiglea: Total Arsenic, Cadmium, and Lead Determination in Brazilian Rice Samples Using ICP-MS. J of Analy Methods in Chemistry 2016; (2016): 1-9.
22. Fernanda C. Pinheiro and Joaquim A. Nóbrega: An overview of sample preparation procedures for determination of elemental impurities in medicines. Microchemical Journal 2022; (175): 107189.
23. Fernanda C. Pinheiro, Ariane I. Barrosand Joaquim A. N obrega: Elemental impurities analysis in name-brand and generic omeprazole drug samples. Heliyon 2020; (6): 03359.
24. Sandhya Kumari, Kritika S Sharma, Meena Nemiwal, Suphiya Khan and Dinesh Kumar: Simultaneous detection of aqueous aluminum (III) and chromium (III) using Perseaamericana reduced and capped silver nanoparticles. Int J Phytoremediation 2022; 24(8): 808-821.
25. Xiao Gu, Siqi Zhu, Linqi Yan, Lei Cheng, Peixi Zhu and Jinqi Zheng: Development of a sample preparation method for accurate analysis of 24 elemental impurities in oral drug products by ICP-MS according to USP/ICH guidelines. J Anal At Spectrom 2021; (36): 512-517.
26. Ming-Juan Zhao, Lei Cheng, Yu-Jia Huang, Ying Tao, Xiao Gu and Jin-Qi Zheng: Establishment and Validation of an ICP-MS Method for Simultaneous Measurement of 24 Elemental Impurities in Ubenimex APIs According to USP/ICH guidelines. Current Pharmaceutical Analysis 2021; 17(6): 723-730.
27. Rajesh Kumar Chawla, Subhranshu Panda, Kulandaivelu Umasankar, Siva Prasad Panda and Dalu Damayanthi: Risk Assessment, Screening and Control of Elemental Impurities in Pharmaceutical Drug Products: A Review. Current Pharmaceutical Analysis 2020; 16(7): 801-805.
28. Bo-Yang Xu, Si-Qi Zhu, Xian-Xin Cheng, YuXu and Ji-Wu Liu: Determination of Total Arsenic, Soluble Arsenic, Total Mercury and Soluble Mercury for a Realgar and Cinnabar-containing Traditional Chinese Medicine Compound Niuhuang Xiaoyan Capsule by Semi-bionic Extraction- ICP-MS. Current Pharmaceutical Analysis 2021; 17: 1-6.
29. Dmitriy Berillo: Comparative Toxicity of Interferon Beta-1a Impurities of Heavy Metal Ions. Medicina (Kaunas) 2022; 58(4): 463.
30. Karizza F. Catenza and Kingsley K. Donkor: Determination of Heavy Metals in Cannabinoid-Based Food Products Using Microwave-Assisted Digestion and ICP-MS. Food Analytical Methods 2022; (15): 2537–2546.
31. Geoffrey A. Dubrow, Rahul S. Pawar, Cynthia Srigley, Jennifer Fong Sam, Christian Talavera, Christine H. Parker and Gregory O. Noonan: A survey of cannabinoids and toxic elements in hemp-derived products from the United States marketplace. Food Analytical Methods 2021; (97): 103800.
32. Sayyed Mohammad Ali Noori: A Comprehensive Review of Minerals, Trace Elements, and Heavy Metals in Saffron. Current Pharmaceutical Biotechnology 2022; (23): 1327-1335.
33. Bayejid Hosen, Abu T.M. Abdullah, T.M. Howlader and Yearul Kabir: Dietary Exposure of Heavy Metals, Minerals and Trace Elements through Cereals Commonly Consumed by Dhaka City Residents. Current Nutrition & Food Science 2020; (16): 815-823.
34. Lakshmi Narasimha Rao Katakam and Hassan Y. Aboul-Enein: Elemental Impurities Determination by ICP-AES / ICP-MS: A review of Theory, Interpretation of Concentration Limits, Analytical Method Development Challenges and Validation Criterion for Pharmaceutical Dosage Forms. Current Pharmaceutical Analysis 2020; (16): 392-403.
    

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    How to cite this article:

    Satish G, Rao TS, Srinivas RK, Suman P, Sridhar B and Divya G: Determination of elemental impurities in eslicarbazepine acetate a partial seizure drug by using ICP-MS. Int J Pharm Sci& Res 2023; 14(8): 3892-04. doi: 10.13040/IJPSR.0975-8232.14(8).3892-04.

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