Analytical Method Development Articles

To ensure compliance with quality and safety standards, the United States, Europe,Japan, and other countries have published compendia, or pharmacopeias, that describe official test methods for many marketed drug products. For example, compendial analytical methods found in United States Pharmacopeia 25 (USP 25) are legally recognized analytical procedures under section 501 (b) of the Federal Food, Drug, and Cosmetic Act. For these compendial methods, USP provides regulatory guidance for method validation (1). In addition, validation of analytical methods is covered by the United States Code of Federal  egulations (CFR). Specific references are 21 CFR 211.165 (e) and 21 CFR 211.194 (a).

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Changes were made to the USP method for the preparation of assay samples of ibuprofen (IBP) tablets (1). These changes included extraction and filtration techniques during sample preparation and required validation for the quantitation of IBP in assay samples. In this article, which is the first in a series about the validation of changes to the USP IBP assay method, we describe the validation of sample extraction and filtration techniques. Specifically, the extraction and filtration validation addresses the following:
● the effect of direct extraction (versus the powdering of tablets
and extraction or the shaking of coated tablets with glass beads
as per USP method) and shaking time on the disintegration
of tablets in extraction solvent and the solubilization of the
active ingredient as determined by the recovery of IBP from
tablets
● the effect of filtration (versus a centrifugation technique as

The sophistication of laboratory analysis instrumentation has advanced steadily over the past few decades.Much to the dismay of the manufacturing industry, this growth has tended to stay in the research arena. Recently, though, instrumentation companies have made strides to bring analytical technology from the laboratory into the pharmaceutical processing line. From the receipt of raw materials to in-process quality control testing, companies are developing unique analytical tools that are intended for easy integration into the pharmaceutical production environment.

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In-process methods are key components of quality control in a chemical manufacturing plant.These methods ensure that a production reaction step conducted by trained operators within the entire validated process will produce a quality chemical entity in the expected yields.The presence of impurities and related compounds (derived from the reaction or secondary reactions) is a critical parameter that determines a synthetic material’s quality.

Capillary electrophoresis has become one of the most advanced separation techniques for pharmaceutical analysis. It is a useful and reliable alternative or complementary technique to liquid chromatography in many areas, including main component assay, impurity determination, enantiomeric separations, identity confirmation and stoichiometry determination. Other areas of interest within the pharmaceutical industry are trace residues determination in cleaning validation and tablet dissolution testing. Numerous validated methods have appeared in the literature, and methods have been included in regulatory submissions by drug companies.

A major advance for capillary electrophoresis (CE) was its recognition by the regulatory authorities. A general monograph on CE is now included in the USP (1), which has also been published in the European (2) and Japanese Pharmacopoeias (3).

A description of immunosorbents, which are solid-phase extraction sorbents based on molecular recognition using antibodies, is provided. The synthesis of immunosorbents for small molecules is discussed the main parameters governing their extraction. The high selectivity these reagents is demonstrated in a number of applications.

Introduction Despite advances in the sensitivity of analytical instrumentation for the end-point determination of analytes in environmental or biological samples, a pretreatment is usually required to extract and isolate the analytes of interest from complex matrices. Solid-phase extraction (SPE) is one such sample preparation technique that has rapidly developed in recent years (1). However, with classic SPE sorbents, such as n-alkylsilicas or highly cross-linked copolymers, retention is based on hydrophobic interactions.

Abstract :Two simple and sensitive validated spectrophotometric methods have been described for the assay of nicorandil in drug formulations. Method A is based on the reaction of the drug with phloroglucinol-sulfanilic acid reagent in sulfuric acid medium to give yellow-colored product, which absorbs maximally at 425 nm. Method B uses the oxidative coupling of 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) with DL- 3,4 - dihydroxyphenylalanine (DL-dopa) in the presence of nicorandil as oxidant in sulfuric acid medium to form an intensely colored product having maximum absorbance at 530 nm. Beer’s law is obeyed in the concentration range 2.5 to 50.0 and 1.0 to 15.0 µg mL–1 with methods A and B, respectively. Both methods have been successfully applied for the analysis of drug in pharmaceutical formulations. The reliability and the performance of the proposed methods are established by point and interval hypothesis and through recovery studies.

Abstract  :The objective of this study was to demonstrate the use of transmission Fourier transform near-infrared (FT-NIR) spectroscopy for quantitative analysis of an active ingredient in a translucent gel formulation. Gels were prepared using Carbopol 980 with 0%, 1%, 2%, 4%, 6%, and 8% ketoprofen and analyzed with an FT-NIR spectrophotometer operated in the transmission mode. The correlation coefficient of the calibration was 0.9996, and the root mean squared error of calibration was 0.0775%. The percent relative standard deviation for multiple measurements was 0.10%. The results prove that FT-NIR can be a good alternative to other, more time-consuming means of analysis for these types of formulations.


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Accuracy is one of several data elements required for assay validation. In a regulated pharmaceutical laboratory, determining accuracy can take on many diff e rent forms. This month’s installment of “Validation Viewpoint” focuses on ways to measure and documentn past “Validation Viewpoint” columns and other publications, we have discussed different methods of quantitation as a distinct and decided part of method validation (1–4). And while many factors are taken into account when validating a method, the determination of the method’s accuracy is an integral part of validating any quantitative method. Accuracy is defined as the closeness of the test results obtained by the method of i n t e rest to the true value, demonstrated a c ross the range of analyte levels expected to be found in samples during routine analyses (5).