MODERN ANALYTICAL TOOLS FOR THE DETERMINATION OF THE ACTIVE PHARMACEUTICAL INGREDIENTS: A REVIEWHTML Full Text
MODERN ANALYTICAL TOOLS FOR THE DETERMINATION OF THE ACTIVE PHARMACEUTICAL INGREDIENTS: A REVIEW
Chavan and R. Gandhimathi *
Department of Pharmaceutical Chemistry and Analysis, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS), Pallavaram, Chennai, Tamil Nadu, India.
ABSTRACT: Discovery of the drug molecule which has therapeutic values is the backbone of drug development. Pharmaceuticals have an important role in the prevention and treatment of diseases in humans and animals. However, gradual change in the process of drug synthesis from drug development to bulk production is a common complication in the drug development process. This change may result in the formation of impurities. Moreover, impurities can also be formed during transport and storage. The presence of more than the prescribed limit of impurities in the drugs may influence the purpose of the pharmaceuticals. Therefore, the evaluation of pharmaceutical drugs for the identification and quantification of impurities at various stages is essential. Several chemical and instrumental methods are used to assess the impurities. For this purpose, analytical instrumentations and methods play a crucial role. The current review highlights the development of impurities at various stages of drug development and pharmaceutical manufacturing. Moreover, this review put light on the recent advancement in the analysis of pharmaceuticals.
Keywords: Active pharmaceutical ingredient, Drug development, High-performance Liquid chromatography, Pharmaceutical analysis
INTRODUCTION: In the development of pharmaceuticals, chemistry, pharmacology, and clinical sciences have played an important role. Drug discovery guided by chemistry, pharmacology, microbiology, and biochemistry has established a standard in research. The discovery of the drugs is not only dependent on the imagination of the chemist but the exchange of ideas between biologists and chemists 1. Innovation of the drug molecules which has therapeutic values is the mother of drug development 2.
Prior to new drug innovation, the investigation on the pre-drug discovery is based on understanding the initial cause of the disease to be treated, alteration of the genes in the disease condition, interacting proteins, and affected cells. Depend upon these facts; the molecule is developed to interact with the affected sites and become drug molecule 1. These molecules are also known as active pharmaceutical ingredients (APIs) 2.
Development of a new drug from an original idea to the launch of the finished product is a complex process that can take 12-15 years and cost around 1 billion USD. In the drug development process, various steps are involved, which are shown in Fig. 1. The time required for the early synthesis of API molecule to the successful submission for registration of new drug is more. During this procedure, various obstacles must be taken into considerations, and numerous entanglements may emerge. The gradual change in the process of drug synthesis is a well-known complication during development. Hence this may lead to a change in the impurity profile of the APIs. Such changes may produce major consequences, including difficult interpretation of toxicological and clinical studies 3. The presence of impurities in APIs can have a significant impact on the quality safety of the products. Therefore, synthesis, characterization, and analysis of such molecules provide unique data regarding safety and therapeutic efficacy, which is required for the identification of drug candidates for further detailed investigations 2. Moreover, in the pharmaceutical research field, the analytical assessment of bulk drug materials, intermediates, drug products, drug formulations, impurities, degradation products, and biological samples containing the drugs and their metabolites is very important. Therefore, monographs were established to characterize the quality of the bulk drug materials by setting a limit to their active ingredient content. Furthermore, from the drug development process to marketing, analytical techniques have an essential role in assessing the physicochemical stability of the drug, selection and design of the dosage form, quantitation of the impurities, and identification of the excess impurity to assess the toxicity profile 2. This review highlights the various sources of impurities in the APIs and the role of various modern analytical techniques in determining the APIs.
FIG. 1: SCHEMATIC REPRESENTATION OF DRUG DEVELOPMENT PROCESS
Sources of Impurities: The regulatory authority around the world, including the United States Food and Drug Administration (FDA) require that the drug substance and drug products should contain the impurities at the levels recommended by the International Conference on Harmonization (ICH) 4. The sources of impurities depend on the quality of the starting materials, reagents, and solvents used during the synthesis, chemical reactions, reaction conditions, purification steps, and storage of the final product. Any change in the mentioned conditions may change the impurity profile of APIs 1.
Synthesis-related Impurities: Raw materials, solvents, intermediate and by-products are the main sources of the impurities in a drug substance during synthesis. Generally, the raw materials are manufactured at a lower purity requirement than the drug substance. Therefore, row materials can contain a number of components that can affect the purity of the drug substance. Similarly, the impurity present in the solvents may range from trace levels to a significant amount which can react with other chemicals used in the synthesis and can result in the formation of other impurities 1. Intermediates are also not generally held to a purity level of the drug substance.
Therefore, guidelines are issued for the use of materials in the synthesis. The prediction of the by-products in the final drug product is not possible. The removal of the intermediate from the final product is costly and time-consuming, and its presence may cause impurity generation due occurrence of simultaneous reactions. In pharmaceutical synthesis, the final intermediate is controlled by regulatory impurity testing 1.
Formulation-related Impurities: Interaction between drug and excipients used in the formulation can cause the generation of impurities in the final drug product. Moreover, during formulation process drug substance is subjected for a various condition which may produce degradation or other deleterious reactions such as heat degenerates thermolabile substances. Solution and suspension are commonly degraded by solvolysis or hydrolysis, respectively. Similarly, in solid dosage forms (tablet and capsule) water and other solvents are used for the granulation; therefore, solvolysis or hydrolysis can also occur.
Oxidation of the pharmaceutical ingredients or drug can act as a source of impurity in the final product. Similarly, light-sensitive materials can undergo photochemical reactions 1.
FIG. 2: DECISION TREE FOR IDENTIFICATION AND QUALIFICATION OF IMPURITIES
Degradation-related Impurities: The degradation of the API on storage can result in the formation of impurities. Hence, stability studies have an important role in prediction, evaluation and ensuring drug product safety 5. These studies include assessment of API stability, compatibility of API with excipients, acceleration stability studies, stability of the final product, kinetic studies, and prediction of the expiry date, and routine stability studies of drug products on marketed sample or dispensed package under various conditions of temperature, light, and humidity 1. It is necessary to perform all the investigations on appropriate reference standards of drug and impurities to get meaningful specifications 1. The assay methods in the monographs of the pharmacopoeia consist of mainly titrimetric, spectrometry, chromatography, and capillary electrophoresis 6-7. These analytical methods based on proper analytical instrumentation must be employed to quantitate drug substance and their impurities Fig. 2.
Titrimetric Methods: In the year 1835, Gay-Lussac invented the volumetric method for analysis which is subsequently known as titration. Recent modernization of titration methods such as the non-aqueous titration method, which can be expanded to weak acid and bases, is commonly used in drug analysis. In most methods, an endpoint is determined by potentiometrically; hence, the precision of the methods is high. In functional group analysis procedures, titrimetric methods are useful in the determination of kinetic measurement (rate of reaction). The advantages of this method including time and labor requirement less, high precision and reference standard are not required 1. This method is recently used to determine potassium sparing diuretic drug candidates, valganciclovir hydrochloride, sildenafil citrate, and aceclofenac sodium 8-11.
FIG. 3: PERCENTAGE OF VARIOUS CHROMATO-GRAPHIC TECHNIQUES FOR ANALYSIS OF IMPURITY IN THE DRUGS
Chromatographic Techniques: For many years, chromatography is the technique of choice for the assessment of the purity of the drugs and products. It is widely used in the pharmaceutical industry 12. Percentage use of various chromatographic techniques for analysis of impurities in drugs is shown in Fig. 3.
High-Performance Liquid Chromatography: In the year 1980, HPLC was first time used for the assay of bulk drugs 3. Further, this method became the main in USP XXVII and to a lesser extent, but widely used method in European Pharmacopoeia 6-7. Among the various chromatography techniques, HPLC is most commonly used in the analysis of the impurities in the drugs as shown in Fig. 1. 3 The selection of appropriate detecting method in HPLC play an important role as it has to detect all the components. UV detector is the most commonly used detector in HPLC; UV detector provides multiple wavelength scanning program, which facilitates monitoring several wavelengths simultaneously. Thus, UV detector guarantee detection of all the components; however, the quantity of the components should be adequate Fig. 4 1.
FIG. 4: USAGE OF VARIOUS DETECTORS IN HPLC ANALYSIS OF DRUGS
A photodiode array (PDA) is a lined array of discrete photodiode on an integrated circuit chip for spectroscopy. PDA is fixed on the image plane of the spectrometer, which provides simultaneous detection of various wavelengths. In this detection method, depending upon components to be identified, the wavelength can be predetermined; hence, a compound that absorbs in a given wavelength can be identified in a single assessment. In contrast with PDA, in a variable wavelength detector, multiple sample injection is required along with a change in wavelength to detect all the peaks. PDA can also be used in the assessment of purity by comparing matching spectra within a peak 1.
It is used in the method development of enalapril maleate 13. Analytes such as alcohol, sugar, carbohydrates, fatty acids, etc., has restricted or no UV absorption; in such case refractive index detector is used. The sensitivity of this is lower compare to other detectors; however, it is appropriate at high analyte concentration 1. A study has reported the use of a refractive index detector in pharmaceutical formulations 14. Among various liquid chromatographic detectors, fluorescence detector is the most sensitive detector (10-1000 times more sensitive than UV detector) for strong UV absorbing material used as an advantage in the measurement of specific fluorescence species samples. This detector has important role in the assessment of pharmaceuticals 15.
Revers phase chromatography with UV detector is the method of choice due to this combination provide better reliability, reproducibility, sensitivity and analysis time. The use of various detectors in HPLC analysis is shown in Fig. 5 3. Despite the various advantages of HPLC, it has its own limitations such as the cost of column is high, more solvent required, and lack of long term reproducibility due to propriety column packing 3. From the last decade of 20th century, a combination of liquid chromatography and mass spectroscopy has emerged as method of choice in drug analysis in both quality control and assurance 16-17.
Reversed-Phase High-Performance Liquid Chromatography: Reversed-phase high-performance liquid chromatography (RP-HPLC or RPLC) consists of polar mobile phase and non-polar stationary phase 18. The isolation of the components depends on the hydrophobic binding of the solute molecule (present in the mobile phase) to the immobilized hydrophobic ligands (stationary phase) Fig. 5. 19.
This method of separation is considered a gold standard in pharmaceutical analysis. The silanol activity of the stationary phase of RPLC should be inhibited to facilitate proper analysis of basic drugs; such drugs may react with negatively charged silanols resulting in broadening of peak and tail 18. Recently, Ergen H. et al. showed linearity, accuracy, precision, specificity, robustness, solution stability, and system stability for assay of polyvinyl alcohol in ophthalmic solution by RP-HPLC 20.
FIG. 5: DIAGRAMMATIC PRESENTATION OF THE ATTACHMENT OF PEPTIDE AND PROTEIN TO RP-HPLC
Ultra-high Performance / pressure Chromato-graphy: In the early 2000s, there was a need for improved liquid chromatography performance in terms of throughput and resolution in pharmaceutical industries. Therefore, UHPLC was developed in the year 2004. It consisted packed column with particles of sub-2µm along with chromatographic assembly, which provides pressure stability up to 1000 to 1500 bar. In the drug discovery and development process, high productivity and less cost are required in quality control, pharmacokinetics, and drug metabolism analysis process. In such conditions, UHPLC can be performed typical pharmaceutical separation in 2-10 min intervals, and the complete method can be developed in 1-2 days. UHPLC decreases analysis time by 5-9 times than conventional HPLC 21. Recently, this method was used in the assay of captopril; similarly, UHPLC with mass spectroscopy is also reported in the analysis of chemical constituents of crude drug 22-23.
Supercritical Fluid Chromatography: Supercritical fluid chromatography (SFC) is an analytical technique developed in the year 1960s. When a liquid is heated with increased pressure beyond its critical point, it shows a particular behavior as chromatographic eluent 24. Diffusivity and viscosity of such fluids is act as gas leading to a high kinetic performance at lower pressure, while the density and solvating power are equivalent to that of liquid, providing good solubility of the analytes. Despite this, the use of gas and liquid chromatography is predominant than SFC in the pharmaceutical industry 18.
However, for the last five years, SFC having an interest in the analytical process in the pharmaceutical community. This is due to significant modification of mobile phase components and composition, use of new stationary phase, and commercialization of state of the art system with a design that is based on the recent UHPLC instrumentation. It was providing improved instrument reliability and performance.25 Studies have reported the use of UHPLCSFC in the pharmaceutical drug analysis 26-28
Hydrophilic Interaction Chromatography: Hydrophilic interaction chromatography (HILIC) is considered as an alternative method for RPLC for polar and ionizable drugs which cannot be retained by RPLC, such as metabolites and another biologically relevant compound. In this technique, the stationary phase hydrophilic in nature, and the mobile phase consisted of a polar aprotic solvent with water and salted 18. The advantages of HILIC, including its action, are similar to the RPLC. The retention of hydrophilic substances is better. It requires less column backpressure, and its sensitivity increases with mass spectroscopy (MS) 29. Currently, it is used in the assessment of polar substances, which cannot be analyzed by RPLC, such as anticancer drugs 30-31.
Combination of Liquid Chromatography with Mass Spectroscopy Devices (LC-MS): MS is the most needed technique in pharmaceutical industries, including research, analysis, development, and manufacturing. The high-resolution MS is used in structural elucidation, while low-resolution MS is useful in routine assessment applications. Miniaturized low-resolution MS is used as a benchtop size MS system 32-33. This system is used for the assessment of reactions in the pharmaceutical process and drug discovery. Literature suggested the use of MS in forensic sciences, pharmaco-kinetics, determination of bioavailability and bioequivalence study, determination of molecular weight, and determination of assay of drug and intermediates 34.
The use of a compact MS analyzer in LC (LC-MS) also involves the identification and quantification of APIs and their degradation products or trace impurities as reported for the analysis of a mixture of loratadine 35. A study was found in which MS detector was implemented in the HPLC/UHPLC equipment.
UHPLC-UV/MS was compared with HPLC-UV for the impurity profiling of APIs such as peptides, bleomycin sulphate, tyrothricin, vancomycin HCL, and bacitracin peptide.
Results showed UHPLC produces increased resolution and decreased limit of detection and in run time. Moreover, MS detectors facilitate direct identification of impurities and components without the need for reference standard 36.
Single-crystal and Powder X-ray Diffraction (XRD): X-ray diffraction methods comprise the predominant tool used for the characterization of pharmaceutical powders.
Single-crystal X-ray diffraction (SXRD) is a technique used for the determination of the solid-state structures at an atomic level, while powder X-ray diffraction (PXRD) is mainly used for identification purposes since crystalline powders exhibit characteristic sharp peaks.
Currently, software programs such as Malvern Panalytical’s XRD software suite and Diffrac. Suite Topas (Bruker AXS, Karlsruhe, Germany) allow structural determination and refinement based on Rietvield refinement.
They are also routinely used to assess the yield of the product by being able to quantify the percentage of crystals and their components in a mixture.
A drawback is that a single pharmaceutical crystal that is qualified for SXRD testing cannot always be produced. Therefore, powder X-ray diffraction (PXRD) is utilized more frequently to verification Fig. 6 37-39.
FIG. 6: POWDERED X-RAY DIFFRACTOGRAM OF PURE ONDANSETRON
Raman Spectroscopy: In the year 1928, Raman and Krishnan invented Raman spectroscopy. This technique involves exposure of monochromatic radiation to samples resulting in the molecular vibration of chemical structures of a substance 40-41. In the pharmaceutical industry, it is an excellent tool for the identification of drugs. This including product development and the real-time monitoring of the production process by Process Analytical Technology 40, 42-43. This technique has advantages such as it is non-invasive, solvents are not required, ease of handling, analysis can be performed without any preparations, and availability of portable equipment can produce results in seconds 41-43. Along with the conventional Raman dispersion phenomenon, various variants are available with diverse applications Table 1 44-54.
TABLE 1: VARIANTS OF RAMAN SPECTROSCOPY AND THEIR APPLICATIONS
|Conventional Raman scattering||Non-destructive, little or no sample preparations, short analysis time||API quantification and characterization of tablets|
|Fourier transform-Raman||Simultaneous measurement at all wavelengths, improved sensitivity||API quantification in powder mixture|
|Resonance Raman spectroscopy||Required less sample||API with less concentration|
|Surface enhanced Raman spectroscopy||Sensitive, can determine the concentration of target molecules in unknown systems||Quantifies highly complex samples and target molecules in unknown systems.|
|Spatially offset Raman spectroscopy||Isolation of chemically rich spectral data from sub surfaces, substructures, layers and through other types of barriers. Quantifies chemical markers. Readings can penetrate container||Samples inside packs and samples for medical diagnostics|
|Coherent anti-Stokes Raman spectroscopy||Label-free, chemically specific signal, fast data-acquisition time and inherent non-destructive “confocal”- like imaging.||Characterizes raw materials, tablets and powder mixtures|
|Stimulated Raman Scattering||Increased sensitivity, because it is free of limitations from labeling and applicable to spot reduction effect||Characterizes multiple excipients distributions in tablets. Mapping of samples as cells and tissues|
|Tipenhanced Raman scattering||Spatial resolution required for nanoscale characterization. Ability to spectroscopically map surfaces||Characterization of materials at nanoscale|
|Raman Micro spectroscopy||Acquire more representative spectra of the sample mixtures; The wide area illumination and/or reduced particle size allows for more accurate measurements of polymorphs||Quantification of polymorphic mixtures, API content in tablets and powder mixtures|
|Low-frequency Raman||Low-maintenance cost, flexible experimental setup and rapid measurement time||Characterization of solid-state forms and their transformations, Imaging of solid dosage forms, Monitoring of solubilization/dissolution processes|
CONCLUSION: Drugs are used to treat or prevent disease or illness in humans. Therefore, drugs must be free from impurities, which can be harmful to humans. Nowadays, it is a mandatory requirement in various pharmacopeias to know the impurities present in APIs. The current review was aimed to study the recent trends in pharmaceutical analysis instruments. It describes the titrimetric techniques methods, HPLC, RP-HPLC, UHPLC, Supercritical Fluid Chromatography (SFC), Hydrophilic interaction Chromatography, LC-MS, XRD, Raman Spectroscopy. The review also highlights the sources of impurities and modern, modified techniques for the analysis of pharmaceuticals.
CONFLICTS OF INTEREST: Nil
- Siddiqui MR, AlOthman Z, and Rahman N: Analytical techniques in pharmaceutical analysis: A review. Arabian Journal of Chemistry 2017; 10: S1409-21.
- Velagaleti R, Burns PK and Gill M: Analytical Support for Drug Manufacturing in the United States-from Active Pharmaceutical Ingredient Synthesis to Drug Product Shelf Life. Therapeutic Innovation & Regulatory Science 2003; 37(4): 407-38.
- Haque SM and Ratemi ES: Drug development and analysis review. Pharmaceutical Chemistry Journal 2017; 50: 837-50.
- Guideline ICH: Impurities in new drug substances Q3A (R2). InProceedings of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva, Switzerland 2006; 25.
- Venkataraman S and Manasa M: Forced degradation studies: Regulatory guidance, characterization of drugs, and their degradation products-a review. Drug Invention Today 2018; 10: 138-46.
- European pharmacopoeia: Fourth Edition 2002.
- United States Pharmacopoeia: Near infra-red spectrophotometry, USP 26 NF 2003; 21: 2388.
- Ivanov A, Smırnov I, Murashko T, Trusova M and Stepanova E: Novel and validated non-aqueous titrimetric method for determination of perspective potassium-sparing diuretic drug candidate in pure form and pharmaceutical formulation. Malaysian Journal of Analytical Sciences 2021; 25: 95-04.
- Abdulrahman SA, Algethami FK, Qarah NA, Basavaiah K and El-Maaiden E: Development of non-aqueous titrimetric and spectrophotometric methods for the determination of valganciclovir hydrochloride in bulk drug and tablets. InAnnales Pharmaceutiques Françaises. Elsevier Masson 2021.
- Seadahmed MS, Adam ME and ELimam TE: Development of acid–base titrimetric method for determination of sildenafil citrate in bulk and tablets forms 2018; 7: 41-7.
- Shuchi J, Mohit C, and Chintaman K: Titrimetric Analysis of Acelofenec Sodium by using Mixed Solvency. International Journal of Trend in Scientific Research and Development 2019; 3:746-8.
- D’Atri V, Fekete S, Clarke A, Veuthey JL, and Guillarme D: Recent advances in chromatography for pharmaceutical analysis. Analytical Chemistry 2018; 91: 210-39.
- Logoyda L, Abdel-Megied AM, Kondratova Y, Trofimenko O, Korobko D and Dakhym I: Development and validation of HPLC method for the simultaneous determination of enalapril maleate in present of their impurities: application to tablet analysis. International Journal of Applied Pharmaceutics 2018; 7: 98-102.
- Gamal M and Elhalim LM: Novel Eco-friendly HPLC Methods Using Refractive Index Detector for Analysis of Three Veterinary Antibiotics in Pharmaceutical Formulations and Rat Plasma. Journal of Chromatographic Science 2020; 58: 940-50.
- Vickrey TM: Liquid chromatography detectors. CRC Press 2020 Oct 28.
- Tassi M, De Vos J, Chatterjee S, Sobott F, Bones J and Eeltink S: Advances in native high‐performance liquid chromatography and intact mass spectrometry for the characterization of biopharmaceutical products. Journal of Separation Science 2018; 41: 125-44.
- Wong AL, Xiang X, Ong PS, Mitchell EQ, Syn N, Wee I, Kumar AP, Yong WP, Sethi G, Goh BC and Ho PC: A review on liquid chromatography-tandem mass spectrometry methods for rapid quantification of oncology drugs. Pharmaceutics 2018; 10: 221.
- D’Atri V, Fekete S, Clarke A, Veuthey JL, and Guillarme D: Recent advances in chromatography for pharmaceutical analysis. Analytical chemistry 2018 Nov 8; 91:210-39.
- Yabré M, Ferey L, Somé IT, and Gaudin K: Greening reversed-phase liquid chromatography methods using alternative solvents for pharmaceutical analysis. Molecules 2018; 23: 1065.
- Ergen H, Guleli M, Sener C, Caliskan C, Semiz S and Ozbek M: Development and validation of a novel reversed phase high performance liquid chromatography with refractive index detector method for assay of polyvinyl alcohol in an ophthalmic solution. Current Pharmaceutical Analysis 2020; 16: 867-71.
- Rathod RH, Chaudhari SR, Patil AS and Shirkhedkar AA: Ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) in practice: analysis of drugs and pharmaceutical formulations. Future Journal of Pharmaceutical Sciences 2019; 5: 1-26.
- Logoyda L: Ultra-high-performance liquid chromatography as an assay method for the investigation of conditions of captopril extraction by organic solvents. Asian Journal of Pharmaceutics (AJP): Free full text articles from Asian J Pharm 2018; 12.
- Han Y, Zhang A, Sun H, Zhang Y, Meng X, Yan G, Liu L, and Wang X: High‐throughput ultra-high performance liquid chromatography combined with mass spectrometry approach for the rapid analysis and characterization of multiple constituents of the fruit of Acanthopanax senticosus (Rupr. et Maxim.) Harms. Journal of Separation Science 2017; 40: 2178-87.
- West C: Recent trends in chiral supercritical fluid chromatography. TrAC Trends in Analytical Chemistry. 2019; 120: 115648.
- Tarafder A: Metamorphosis of supercritical fluid chromatography to SFC: an overview. TrAC Trends in Analytical Chemistry 2016; 81: 3-10.
- Plachká K, Švec F,and Nováková L: Ultra-high performance supercritical fluid chromatography in impurity control: Searching for generic screening approach. Analytica Chimica Acta 2018; 1039: 149-61.
- Plachká K, Khalikova M, Babičová B, Němcová Z, Roubíčková L, Jung O, Svec F and Nováková L: Ultra-high performance supercritical fluid chromatography in impurity control II: Method validation. AAC 2020.
- Lemasson E, Bertin S, Hennig P, Lesellier E and West C: Comparison of ultra-high performance methods in liquid and supercritical fluid chromatography coupled to electrospray ionization–mass spectrometry for impurity profiling of drug candidates. Journal of Chromatography A 2016; 1472: 117-28.
- McCalley DV: Understanding and manipulating the separation in hydrophilic interaction liquid chromatography. Journal of chromatography A 2017; 1523: 49-71.
- Xie F, Colin P and Van Bocxlaer J: Zwitterionic hydrophilic interaction liquid chromatography-tandem mass spectrometry with HybridSPE-precipitation for the determination of intact cisplatin in human plasma. Talanta 2017; 174: 171-8.
- Amasya G, Gumustas M, Badilli U, Ozkan SA, and Tarimci N: Development of a HILIC method for the determination of 5-fluorouracil from nano drug delivery systems and rat skin extracts. Journal of Pharmaceutical and Biomedical Analysis 2018; 154: 285-93.
- Swales JG, Hamm G, Clench MR and Goodwin RJ: Mass spectrometry imaging and its application in pharmaceutical research and development: A concise review. International Journal of Mass Spectrometry 2019; 437: 99-12.
- Bu X, Regalado EL, Hamilton SE and Welch CJ: The emergence of low-cost compact mass spectrometry detectors for chromatographic analysis. TrAC Trends in Analytical Chemistry 2016; 82: 22-34.
- Pratima NA, and Gadikar R: Liquid Chromatography-Mass Spectrometry and Its Applications: A Brief Review. Archives of Org and Inorganic Chem Sci 2018; 1:26-34.
- Bu X, Yang J, Gong X and Welch CJ: Evaluation of a compact mass spectrometer for routine support of pharmaceutical chemistry. Journal of Pharmaceutical and Biomedical Analysis 2014; 94: 139-44.
- D’Hondt M, Gevaert B, Wynendaele E and De Spiegeleer B: Implementation of a single quad MS detector in routine QC analysis of peptide drugs. Journal of Pharmaceutical Analysis 2016; 6: 24-31.
- Ghadiri M, Ning Z, Kenter SJ and Puik E: Attrition of granular solids in a shear cell. Chemical Engineering Science 2000; 55: 5445-56.
- DallaValle JM: Micromeritics: the technology of the particles. Pitman Publishing Corporation 1943.
- Aulton ME and Taylor KM: Aulton's Pharmaceutics E-Book: The Design and Manufacture of Medicines. Elsevier Health Sciences 2017.
- Paudel A, Raijada D and Rantanen J: Ramanspectroscopy in pharmaceutical product design. Adv Drug Deliv Rev 2015; 89: 3-20.
- Depciuch J, Kaznowska E, Zawlik I, WojnarowskaR, Cholewa M, Heraud P and Cebulski J: Application of Raman Spectroscopy and Infrared Spectroscopyin the Identification of Breast Cancer. Applied Spectrosc 2016; 70: 251-63.
- Wang H, Boraey MA, Williams L, LechugaBallesteros D, and Vehring R: Low-frequency shiftdispersive Raman spectroscopy for the analysis ofrespirable dosage forms. Int J Pharm 2014; 469: 197-05.
- Be̅rziņš K, Fraser-Miller SJ and Gordon KC: A new frontier for nondestructive spatial analysis of pharmaceutical solid dosage forms: spatially offset low-frequency raman spectroscopy. Analytical Chemistry 2021; 93: 3698-05.
- Zhu X, Xu T, Lin Q and Duan Y: Technical development of raman spectroscopy: From instrumental to advanced combined technologies. Appl Spectrosc Rev 2014; 49: 64–82.
- Casian T, Reznek A, Vonica-Gligor AL, Van Renterghem J, De Beer T and Tomuță I: Development, validation and comparison of near infrared and Raman spectroscopic methods for fast characterization of tablets with amlodipine and valsartan Talanta 2017; 167: 333-43.
- Dzsaber S, Negyedi M, Bernáth B, Gyüre B, Fehér T, Kramberger C, Pichler T and Simon F: A Fourier transform Raman spectrometer with visible laser excitation. J. Raman Spectrosc 2015; 46: 327-32.
- Griffen JA, Owen AW and Matousek P: Development of Transmission Raman Spectroscopy towards the in line, high throughput and non-destructive quantitative analysis of pharmaceutical solid oral dose. Analyst 2015; 140: 107-12.
- Zhang Y and McGeorge G: Quantitative Analysis of Pharmaceutical Bilayer Tablets Using Transmission Raman Spectroscopy. J Pharm Innov 2015; 10: 269-80.
- Villegas Borrero NF, Clemente da Silva Filho JM, Ermakov VA and Marques FC: Silver nanoparticles produced by laser ablation for a study on the effect of SERS with low laser power on N719 dye and Rhodamine-B. MRS Advances 2019; 4: 723-31.
- Höhl M, Roth B, Morgner U and Meinhardt Wollweber M: Efficient procedure for the measurement of preresonant excitation profiles in UV Raman spectroscopy. Rev Sci Instrum 2017; 88.
- Chruszcz-Lipska K, Jaworska A, Szczurek E and Baranska M: (-)-R-mevalonolactone studied by ROA and SERS spectroscopy. Chirality 2014; 26: 453-61.
- Saleh TA, Al-Shalalfeh MM and Al-Saadi AA: Graphene Dendrimer-stabilized silver nanoparticles for detection of methimazole using Surface-enhanced Raman scattering with computational assignment. Sci Rep 2016; 6.
- Zong C, Xu M, Xu LJ, Wei T, Ma X, Zheng XS, Hu R, and Ren B: Surface-Enhanced RamanSpectroscopy for Bioanalysis: Reliability and Challenges. Chem Rev 2018; 118: 4946-80.
- Bērziņš K, Fraser-Miller SJ and Gordon KC: Recent Advances in Low-Frequency Raman Spectroscopy for Pharmaceutical Applications. International Journal of Pharmaceutics. 2020; 120034.
How to cite this article:
Chavan A and Gandhimathi R: Modern analytical tools for the determination of the active pharmaceutical ingredients: a review. Int J Pharm Sci & Res 2022; 13(1): 61-69. doi: 10.13040/IJPSR.0975-8232.13(1).61-69.
All © 2022 are reserved by the International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
A. Chavan and R. Gandhimathi *
Department of Pharmaceutical Chemistry and Analysis, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS), Pallavaram, Chennai, Tamil Nadu, India.
25 December 2020
16 May 2021
29 May 2021
01 January 2022