Impurity

In the pharmaceutical industry an impurity is considered, defined the any other organic material besides the drug substance or pharmaceutical ingredients.  The impurity may be formed during the formulation or upon aging of two APIs in medicines. Stability testing is an integral part of pharmaceutical development. The primary purpose of stability testing is to provide supporting evidence on stability behavior of pharmaceutical drug products. Stability is the capacity of a drug product to remain within specifications established to ensure its identity, strength, quality and purity.

The impurities in pharmaceuticals are unwanted chemicals that remain with the active   pharmaceutical ingredients (APIs). Impurities plays a major role in pharmaceuticals therefore profiling of impurity is very important. The pharmaceutical impurities are the unwanted chemicals that remain or are generated during the manufacturing process. These impurities are classified into three main categories such as organic, inorganic and residual solvents. Organic impurities include intermediate, starting material, degradation products, reagents, ligands, catalyst and by products. Whereas inorganic impurities are heavy metals, residual solvent, inorganic salt, filter, aids, charcoal and reagents. Impurity profiling helps in detection, identification and quantification of various types of impurities. It is a best way to characterize quality and stability of bulk drugs and pharmaceutical formulations. Due to rapid development of the analytical methodology it is imperative to review problems related to impurities present in the drug substances and drug products with their solutions. Various regulatory authorities like ICH, USFDA TGA, WHO, ANVISA, Canadian Drug and Health Agency are emphasizing on drug substance and drug product purity requirements and on identification of impurities in active pharmaceutical ingredients as presence of impurities even in small amounts may influence the efficacy and safety of the pharmaceutical products. Thus enlightening the need of impurity profiling of drug substances in pharmaceutical research this review focuses on various classification for identification as well as quantification of impurities present in the pharmaceuticals. The analytical techniques used for impurity profiling of drugs are LC-MS-MS, LC-NMR, LC NMR- MS, GC-MS, and LC-MS, DSC, TGA, ICP-MS, IC, HPLC and GC.

In the pharmaceutical industry an impurity is considered, defined the any other organic material besides the drug substance or pharmaceutical ingredients.  The impurity may be formed during the formulation or upon aging of two APIs in medicines. The highly sophisticated instrumentation, such as mass spectra meters attached to the gas chromatography or HPLC in various matrices. GC is the most useful technique for identification of residual solvent. The advent of hyphenated technique has revolution any impurity profiling, by not only separation but structural identification of impurities as well among all techniques. The most exploited techniques for impurities profiling of drug are LC-MS-MS, LC-NMR, LC-NMR-MS, GC-MS AND LC-MS.

To develop rapid, rugged, precise and an accurate stability indicating analytical method for estimation of related substances in Ursodeoxycholic Acid tablets. The separation of impurities and Ursodeoxycholic Acid drug is achieved by an isocratic chromatographic method on C18, 250 mm x 4.6 mm, 5µm column. The mobile phase consists of buffer, acetonitrile and methanol in the ratio of 35:28:37 v/v/v pumped at a flow rate of 1.0 ml/minute 35:37:28v/v/v pumped at a flow rate of 1.0 ml/minute. The detection was carried out by using refractive index (RI) detector. The proposed chromatographic method was validated and found to be linear over the concentration range from LOQ to 150.0% of impurity limit level.  Overall mean recovery of Chenodeoxycholic acid impurity was found to be 100.6±4.0%w/w The method was found to be simple, stability indicating, precise, accurate and robust which can be utilized for estimation of related substances in Ursodeoxycholic Acid tablets

The aim of present work was to develop an accurate, precise, reproducible and economical UV spectrophotometric method for estimation of 1H, 1’-H-2, 2’-Bibenzimidazole Impurity In Telmisartan Bulk and Formulation. This method was based on area under curve of UV spectrum between 235 to 254 nm and validated as per ICH guideline Q2 (R1). The method has followed linearity in the range of 5-30μg/ml. The value of correlation coefficient was 0.998. Satisfactory values of Percent relative standard deviation for the intra-day and inter-day precision indicated that method is precise. Results of the recovery studies (97.63% to 98.66 %) showed accuracy of the method. LOD and LOQ were calculated as 0.3221μg/ml and 0.9761 μg/ml, respectively. The developed method can be used for routine estimation of 1H, 1’-H-2, 2’-Bibenzimidazole Impurity In Telmisartan Bulk and Formulation.

This research is directed towards Synthesis and quantitation of process-related impurity in Felodipine bulk and formulation. The synthesis of 1,4-Dihydro-2,6-Dimethyl-4-(m- chloro phenyl) pyridine-3,5 Dicarboxylate was identified, characterized, developed and validate by using various analytical techniques such as UV, IR, NMR  for the assessment of impurities in the bulk and formulation in Felodipine. The synthesis of of 1,4-Dihydro-2,6-Dimethyl-4-(m- chloro phenyl) pyridine-3,5 Dicarboxylate was performed by Hantzch pyridine synthesis, by using m-chlorobenzaldehyde, ethylacetoacetate, in presence of ammonia and methanol as a catalyst. The percentage yield was observed to be 80.29%. The preliminary evaluation was performed via melting point, elemental analysis and thin layer chromatography (TLC). Melting point of obtained synthesised compound was noticed to be 134-1370C, whereas Rate of flow ( Rf) value was estimated and found to be 0.70. The TLC of impurity was performed by using Benzene and Methanol (6:1). The structure confirmation of obtained synthesized impurity by using sophisticated analytical instrument viz, Fourier transform infra red( FT-IR), nuclear magnetic resonance (NMR) and ultra violet (UV) spectroscopy. The method was validated as per ICH guidelines and was found to be linear, precise, robust, accurate, rugged.