What is the difference between the purity and potency of drug substance

In Oxidation conditions, hydrogen peroxides are extensively exercised. The oxidative degradation of drug substances involves an electron transfer mechanism to form reactive anions and cations [95].

Functional group with labile hydrogen like benzylic carbon, allylic carbon, and tertiary carbon or a-positions with respect to hetero atom is prone to oxidations. Photo stability studies are carried out to create mainly primary degradants of drug substances by exposure to UV or fluorescent conditions. Drug substances are exposed to a minimum of 1.

Some of the functional group viz carbonyls, nitro aromatic, N-oxide, alkenes aryl chlorides weak C-H and O-H bonds, sulfides and polyenes are photosensitive [96]. Thermal degradations are studied by exposing drug to dry heat and wet heat. It may possible to carry out thermal degradation by enhancing the temperature for shorter duration of time.

The steps involved in stability-indicating method include sample generation, method development and optimization, method validation [97]. It also includes validation of forced degradation studies carried out with intention;. Table 7 : Stress Condition. The second phase of the analysisinvolved categorizing the major chemical reactions responsible forthe generation of the five most prevalent alertingstructures.

Thistwo-step approach led, in turn, to a proposal for the prediction offunctional groups that may have a propensity to degrade toalerting structures not necessarily present in the parent molecule []. Analytical Method for identification of Impurity. It becomes obligatoryto isolate and characterize impurities in order to monitor them accurately, because approximate estimations of impurities are generally made against the material of drug substance and can be uncorrected.

These estimations are based on the assumption that impurities are structurally related to the material of interest and thus, have the same detector response. Number of methods will be of significance for isolation and characterization of impurities []. Many analytical techniques are used for separation of impurities and characterization of it [ ]. Figure 2 : Analytical Method for identification of Impurities. A general scheme is set up for the estimation of the impurity profile of bulk drug substances by the multifaceted use of chromatographic, spectroscopic and hyphenated techniques.

HPLC is one of exploited chromatographic technique most abundantly referred to identify and separation of impurities. Drug compound were identified on the basis of retention time and direct comparison with known standards. For isolation and identification impurities by HPLC requires column, optimized system and suitable mobile phase system. Specialized instruments are used to carry out HPLC in the preparative mode. Most explored analytical method for separation of impurities includes HPLC.

Table 8: HPLC method for separation of impurities. Gas-Chromatography is a very imperative technique for quantitation. It can provide the desired resolution, selectivity, and ease of quantitation. The primary limitation is that the sample must be volatile or has to be made volatile by derivatization. This technique is very useful for organic volatile impurities.

Table 9: Gas Chromatography. The use of UV-VIS spectroscopy as a tool for the identification and structure elucidation of impurities in drugs without chromatographic separation is of very modest relevance. This method is useful only impurities absorbs specifically in the ultraviolet region above nm. UV-Visible is a technique useful in identification of pure drug compounds. Compounds containing chromophores absorbs specific wavelength of ultraviolet or visible light that is directly related to the concentration of the sample.

Table UV-Visible Spectroscopy method. IR is infrequently used technique for analysis of impurities. FT-IR spectrometry can be functional to resolve the presence or absence of chemically related impurities in raw pharmaceutical substances if their chemical structure is known and are found above as assured limits of percentage in the substance. CE is a practical technique when very low quantities of sample are available and high resolution is required. The primary complexity is relatively lower reproducibility.

Table Capillary Electrophoresis. Supercritical fluid Chromatography. Orthogonal separations using SFC have been explained as recent tool in impurity profiling of pharmaceuticals []. The use of SFC as a technique for drug impurity profiling was studied to define starting conditions in method development for drug impurity profiling.

A set of dissimilar stationary phases was screened in parallel. The possibility to select a set of dissimilar columns using the retention factors k -values for a set of 64 drugs were measured on 27 columns []. The comparison of ultra-high performance methods in liquid chromatography and supercritical fluid chromatography coupled to electrospray ionization- mass spectrometry for impurity profiling of drug candidate have been reported []. The importance and the challenges of impurity profiling in modern pharmaceutical analysis have been discussed [].

Evaluation of mobile phase gradient supercritical fluid chromatography for impurity profiling of pharmaceutical compounds have been studied. The use of gradient supercritical fluid chromatography SFC for the impurity profiling of pharmaceutical products is not widely practiced. Historically, the limited advancement in SFC instrumentation and the lag in column development have resulted in marginal sensitivity, selectivity and reproducibility when compared with high performance liquid chromatography HPLC [].

The quantitative determination of salbutamol sulphate impurities using achiral supercritical fluid chromatography has been studied [].

Table Reported impurity in different pharmacopoeia. The work explained by ICH under the Efficacy heading is dealt with the design, conduct, and safety and also preparing reports of clinical trial which includes types of medicines derived from biotechnological processes. The reason of the guideline is to optimize the standard genetic toxicology battery for prediction of potential human risks, and to provide guidance on interpretation of results, with the ultimate goal of improving risk characterization for carcinogenic effects that have their basis in changes in the genetic material.

Table Threshold [8]. The possibility for mutagenic effect and also damaging DNA by genotoxic impurities and chemical compounds cannot be denied. The genotoxicity tests are performed as in vitro and in vivo tests. Usually, these tests are proposed to identify compounds that create genetic damage by several mechanisms [].

These tests are meant for identification of hazards in concerned with damage to DNA and also its fixation. Damage to DNA can be manifested by several ways viz gene mutations, larger scale chromosomal damage or recombination. It can further be studied for heritable effects and in the multi-step process of malignancy.

The entire process to understand is complex in which genetic changes might possibly play only a part []. There will be a change in chromosomal number which may be linked up with be linked up with tumor genesis.

Carcinogenicity can be predicated by genotoxicity test []. It may possible to identify the potent mutagenic impurities in drug substance when it is checked for conventional mutagenicity investigation. The virtual safety doses for Acrylonitrile 7.

From, this investigation, it can be concluded that the in silico determination of structural liabilities for mutagenicity provides a highly sensitive and conservative method for identification of potentially genotoxic impurities []. In absence of sound literature on additional genotoxicity testing of impurity should be considered typically using bacterial reverse mutation assay Ames test [ ].

The recent year's new strategies arise for dealing with genotoxicity impurities or potential genotoxicity impurities arising from drug synthesis have gained considerable focused. These genotoxic impurities may be crept in as starting material, reagent, intermediate catalyst, by-product, and degradation product or isomer etc [].

As per the guideline of various pharmacopoeia and ICH, the main objective is to suggest acceptable amounts for impurities in pharmaceuticals for the safety of the patient. The guideline describes levels considered to be toxicologically acceptable for some residual solvents. The current phrase permitted daily exposure PDE is defined in the present guidance as a pharmaceutically acceptable intake of residual solvents to avoid confusion of differing values for ADI's of the same substance [].

Genetic toxicology studies are reported in Salmonella typhimurium, Chinese hamster ovary cells, Drosophila melanogaster, mouse bone marrow cells and mouse peripheral blood cells. The in vitro studies can be conducted with and without exogenous metabolic activation from induced S9 liver enzymes []. The aim is safe guarding human health and maintenance of environmental integrity against the possible harmful effects of chemicals generating from long-term environmental exposure. The methods implicated in the estimation of maximum safe exposure limits are generally depends on long-term studies [].

The present review article provides a viewpoint on impurities in drug substance and drug products. It furnishes valuable information about impurities types, its classification, various techniques for isolation and characterization, and also for the determination, qualification of impurities. This knowledge can create ample information about bulk drugs, drug product and guidance for its storage.

Further the article furnishes information regarding the virtual safety limits for solvents and chemicals. Preliminary information about the Genotoxity studies, guidelines and principle is more relevant information described.

Over all discussion provided above about impurity profiling and several associated issues would be of general and broader interest. Authors are thankful to R. Patel Institute of Pharmaceutical Education and Research for providing library facilities.

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Purity testing measures the amount of impurities present in a sample and is expressed as either a fraction or as a percentage. If the sample has low purity, this means it has many contaminants. If the purity is high, there are few contaminants. If you are looking for a laboratory to perform purity and potency assays, call us at , or visit us online to submit a test request! Below are some of the purity and potency test requests we have received and helped facilitate:. Republished by Blog Post Promoter.

October 5, December 17, contractlab1 drug development , pharmacology , purity and potency assays , purity potency assays. Biological purity and potency assays are procedures used by laboratories studying medicine, pharmacology, or other biological process, to assess or measure the presence of a substance.