Impurities

Unwanted materials that coexist with active pharmaceutical ingredients (APIs), surface during formulation, or become apparent after the formulation and API have run out are known as pharmaceutical impurities. The therapeutic properties of generic drugs may be affected, even in minute quantities, by the creation of these chemical pollutants. The pharmaceutical business is currently facing significant issues with impurity control. Researchers from the International Conference on Harmonization (ICH) have worked to manage pollutants. This review describes various impurity types, sources, and degrading transcription factors using specific examples.

In the field of pharmaceutical chemistry, impurities are considered as unwanted chemicals that present in the therapeutically active pharmaceutical compounds. They are unusually potent and expected to produce toxicity; hence it may be shows unexpected pharmacological actions which are harmful to human health. The control of impurities is currently a critical issue to the pharmaceutical industry. The most possible source of impurities is the synthesis that involves various steps, i.e. from starting materials to finished products through the intermediate steps. Impurities in drug substances and drug products are key regulatory issues in the office of generic drugs and have significant impact on the approvability of drugs hence International Conference on Harmonization (ICH) and Food and Drug Administration (FDA) guidelines introduce the identification and qualification procedures for them, by using various analytical techniques like TLC, LC, GC, MS, NMR, IR, UV, GC-MS, LC-MS, LC-NMR etc,.

A novel, simple and rapid reversed-phase liquid chromatography mass spectrometric method (LC-MS) was developed and subsequently used for the characterization of Drotaverine hydrochloride (DRH) and its impurities. The separation was achieved in 22 minutes on Merck Purosphere STAR RP-18e (250 x 4.6) mm, 5 µm column in gradient mode with flow rate 1.5 mL/min. 0.05 M ammonium acetate buffer pH 3.0 and a mixture of acetonitrile and methanol 85:15 v/v  was used as mobile phase A and mobile phase B, respectively. Detection was carried out at the optimum wavelength of 280 nm using a photodiode array/triple quadrupole mass detectors. The retention time of Drotaverine was found about 7 minutes. Specificity of the method was established by blank solution and the extreme degraded sample was used for the detection of impurity masses. The impurities detected under mass detector were further ionized for their daughter ions.

Ramipril is a prodrug of the active metabolite ramiprilat, it inhibits angiotensin-converting enzyme and consequent raise in blood pressure. Its pharmacologic effect aids the treatment of hypertension, congestive heart failure and reduces mortality in post myocardial infarction patients. As for other drugs, Ramipril might degrade upon storage and compromise the quality, efficacy and safety of the product. In order to avoid deterioration, it is important to characterize the degradation products and source of stress (temperature, water content, oxidizers, etc). This review aims to summarize the data concerning the subject and serve as a guide for further studies.

The current practice of characterization and control of impurities in pharmaceuticals is reviewed with emphasis on issues specific to the generic industry. This review includes an overview of FDA, ICH, TGA, TPD and EMEA guidelines related to impurities in Drug Substance and Drug Products. This introduces the identification, characterization and qualification procedures for ANDAs and approaches to the establishment of acceptance criteria for both drug substance and drug product and significance of analytical methods in total process.