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IMPURITY PROFILING: IMPORTANCE, TECHNIQUES, AND GUIDELINES FOR DRUG DEVELOPMENT AND QUALITY CONTROL
Surendar Angothu
Asst. Professor, Department of Pharmacognosy, Princeton College of Pharmacy, Hyderabad, Telangana, India
Boggula Ratnakumari
Asst. Professor, Department of Pharmacognosy, Princeton College of Pharmacy, Hyderabad, Telangana, India
Abstract - The process of collecting and analyzing data to determine an impurity's biological safety is known as impurity profiling. Any organic material that, in addition to the drug substance or its ingredients, arises from synthesis or contains unwanted chemicals that remain in APIs is considered an impurity. The pharmaceutical industry faces a pressing problem right now: keeping impurities under control. Guidelines for controlling impurities were formulated by the International Conference on Harmonization (ICH). The requirements for purity and the detection of impurities in Active Pharmaceutical Ingredients (APIs) are being emphasized by a number of regulatory agencies, including the ICH, the US Food and Drug Administration, and the Canadian Drug and Health Agency. TLC and HPLC are the methods used to identify impurities. The development of hyphenated techniques has revolutionized impurity profiling by separating and structurally elucidating impurities at the same time. For drug impurity profiling, LC-MS-MS, LC-NMR, LC-NMRMS, GC-MS, and LC-MS are the most frequently used methods.
Keywords: Hyphenated Methods, HPLC, impurity profiling, and ICH guidelines.
1 INTRODUCTION
Impurities are defined by ICH as pharmaceutical products; Impurities are substances that are present in the product but are not the API or the excipients that were used to make it.
Thus, impurities are undesirable chemicals that remain in trace quantities within the API or formulation1. It is impossible to avoid the drug substance's trace presence of impurities. They can brought down or change the pharmacological adequacy of dynamic drug fixings (Programming interface). Impurities can occasionally have teratogenic, mutagenic, or carcinogenic effects. As a result, this may be harmful to human health in fetuses; controlling and monitoring impurities in API/pharmaceutical products is becoming increasingly popular. As a result, API impurity profiling is necessary.
The identity and quantity of impurities in pharmaceuticals, or impurity profiling, are currently receiving significant and critical attention from regulatory authorities.
the various pharmacopoeias, including BP and USP. The US Food and Medication Organization (FDA) have embraced the direction arranged under the sponsorship of the ICH. The debasement profile of drugs is of expanding significance as medication security gets increasingly more consideration from people in general and from the media. This topic is covered in a number of recent books and journal reviews, and US and international authorities provide guidelines.
Unless the potential impurities are anticipated to be unusually potent or toxic, it is not considered
Vol. 02, Issue 07,July2017ISSN: 2456-1037 (INTERNATIONAL JOURNAL) UGC APPROVED NO. 48767
2 necessary, according to ICH guidelines on impurities in new drug products, to identify impurities below the 0.1% level. Impurities should always be classified4. Mass spectrometry (MS), nuclear magnetic resonance (NMR), high-performance liquid chromatography (HPLC), and tandem mass spectrometry have all been used to isolate and identify process-related impurities and degradation products in a number of articles for pharmaceutical substances. As a result, an essential component of drug development and regulatory evaluation is the identification, quantification, and control of impurities in the drug substance and drug product.
The various impurities that can be found in APIs, methods for identifying them, and potential ways to deal with the resulting interferences are discussed in this article.
1.1 Portrayal Strategies
Profoundly refined instrumentation, for example, MS joined to a GC or HPLC, are unavoidable devices in the distinguishing proof of minor parts (drugs, contaminations, debasement items, metabolites) in different grids.
Different methods are used to characterize impurities: which include these:
1.2 Nuclear Magnetic Resonance (NMR):12 NMR is a powerful analytical tool for structural elucidation because it can reveal the specific bonding structure and stereochemistry of pharmaceutically relevant molecules. In comparison to MS, which only requires a sample of less than 1 mg, conventional NMR sample requirements are around 10 mg.
1.3 Mass Spectroscopy (MS) Over the past few decades, it has had a growing impact on the pharmaceutical development process. New opportunities for monitoring, characterization, and quantification of drug-related substances in active pharmaceutical ingredients and pharmaceutical formulations have been provided by advancements in the design and efficacy of interfaces that directly connect Mass Spectrometers with separation techniques.
2 VALIDATION OF ANALYTICAL PROCEDURES
The process of confirming that the HPLC procedure used for a particular test is appropriate for its intended use is known as HPLC method validation.
Method validation is an important part of good analytical practice because it can be used to evaluate HPLC results' quality, dependability, and consistency. Strategy approval has gotten extensive consideration in writing and from modern boards of trustees and administrative organizations.
Specificity: The ability to evaluate the analyte without ambiguity in the presence of expected components is known as specificity. Impurities, degradants, matrix, and other topics are frequently examined. It is not always possible to show that an analytical method is unique to a specific analyte (complete discrimination).
Precision: The degree to which the value that is accepted as either an acceptable reference value or a conventional true value is in agreement with the value that is found is what is meant by the accuracy of an analytical procedure.
Accuracy can be evaluated using spiked samples containing known quantities of impurities, and it should
3 be reported as a percentage of recovery (percent recovery is the area obtained by spike the impurity in the sample).
Accuracy: The closeness of agreement between a series of measurements obtained from multiple samplings of the same homogeneous sample under the specified conditions is how an analytical procedure's precision is expressed. The variance, standard deviation, or coefficient of variation of a series of measurements typically represent an analytical procedure's precision.
Continuity: intraassay precision also describes the precision achieved over a brief time period under the same operating conditions.
Advanced precision: demonstrates with laboratory variations: various days, various analysts, various pieces of equipment, etc.
Compatibility: demonstrates the precision between laboratories (collaborative studies, typically used for methodology standardization).
The detection limit: The smallest amount of analyte in a sample that can be detected but not necessarily quantified to an exact value is the limit of detection for a particular analytical method. As far as not entirely set in stone by the examination of tests with known groupings of analyte and by laying out the base level at which the analyte can be dependably recognized. Based on Signal-to-Noise b. Based on Response Standard Deviation and Slope
Quantity Limit or Quantity Limit:
The lowest amount of analyte in a sample that can be quantitatively determined with sufficient precision and accuracy is the limit of quantitation for a particular analytical method. Linearity: The ability of an analytical procedure to yield test
results that are directly proportional to the concentration (quantity) of analyte in the sample within a specified range is known as its linearity.
Sturdiness: An analytical procedure's robustness is a measure of its ability to withstand subtle but deliberate variations in method parameters and indicates its dependability in everyday use.
3 APPLICATIONS
Numerous applications have been sought in the areas of drug designing and in monitoring quality, stability, and safety of pharmaceutical compounds, whether produced synthetically, extracted from natural products or produced by recombinant methods.
4 CONCLUSION
The requirements for purity and the detection of impurities in Active Pharmaceutical Ingredients (APIs) are being emphasized by a number of regulatory agencies, including the ICH, the USFDA, and the Canadian Drug and Health Agency. The process of collecting and evaluating data to determine an impurity's biological safety is known as "qualification of the impurities." thus demonstrating the significance and necessity of drug impurity profiling in pharmaceutical research. Chromatographic and spectroscopic methods can be used by themselves or in conjunction with other methods to identify impurities.
TLC, HPLC, HPTLC, AAS, and other techniques can be used to identify and characterize impurities in a variety of ways. In the field of impurity profiling, conventional liquid chromatography, particularly HPLC, has been extensively utilized; Its numerous applications are due to its sensitivity, cost-effective separation,
Vol. 02, Issue 07,July2017ISSN: 2456-1037 (INTERNATIONAL JOURNAL) UGC APPROVED NO. 48767
4 and wide range of detectors and stationary phases. One of the most popular methods for locating residual solvents is headspace GC. Impurity profiling has been transformed by hyphenated techniques, which not only separate impurities but also identify them structurally. Among all joined strategies, the most taken advantage of procedures, for debasement profiling of medications are LC MS, LCNMR, LC-NMR-MS, GC- MS, and LC-MS. The impurity profiling process is made simple by the precise method development and procedure validation. The concept of quality assurance is vast. This idea brings us to the subject of IMPURITY PROFILING. A substance under investigation's impurity profile gives as much information as possible about its impurities. Manufacturers now have quality standards to meet thanks to the establishment of guidelines for the levels of impurity in drugs and products. The qualification of the impurity profile of a new chemical entity is essential. The pharmaceutical analyst must carefully consider their analytical technology because high dose compounds have a qualification threshold of less than 1%. The development scientists are aware of the significance of qualifying impurity profiles in order to guarantee that the impurities in the batches used in safety studies are taken into account. This field of impurity identification and quantification has advanced from limit tests for impurities. utilizing more recent methods like NMR, GCIR (Gas Chromatography- Infrared Spectrometry), UV spectroscopy with diode array detection, and HPLC. The purpose of this article is to try to comprehend the concept of an impurity profile as well as various
aspects and methods associated with it.
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