Current Pharmaceutical Analysis - Volume 19, Issue 6, 2023

Spectrofluorimetry is an analytical technique with high sensitivity, specificity, and simplicity, and is very economical. Drugs that lack native fluorescence are derivatized with reagents so that highly fluorescent compounds are formed that can be readily detected by spectrofluorimetry. There are different reagents such as 4-chloro-7-nitrobenz-2-oxa-1,3-diazole (NBD-Cl), N- methylnicotinamide chloride (NMNCl), 9-flurenylmethylchloroformate (FMOC-Cl), dansylchloride (DNS-Cl), 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH), 1,2- naphthoquinone-4-sulfonate (NQS), 1,4- benzoquinone, 4-fluro-7-nitrobenzofurazan (NBD-F), ninhydrin, benzoin, N- bromo succinimide (NBS), acetylacetone & HCHO, ortho-phthalaldehyde (OPA), and 2-cyanoacetamide used in spectrofluorimetric determination of the drugs that lack native fluorescence. The present review highlights these reagents with principle, reaction conditions, and their applications.

The production of drugs is very complicated. In the process of preparation and transportation, mixing a small amount of reaction raw materials, intermediates, and storage degradation products is inevitable, which affect the quality of drugs. The quality of drugs not only affects the efficacy, but also produces unpredictable side effects and toxicity, which is directly related to people's life and health. The detection of drug quality has always been the focus of attention. Related substance research is one of the key projects in drug quality research, and its content is a direct indicator of drug purity. Therefore, it is very important to establish the content standard of drug related substances and develop the detection method of related substances. The related substances of drugs are rich in variety, with different physical and chemical properties, and the components of related substances, such as degradation products need further analysis, which makes it difficult to effectively apply the detection methods. After years of research, the detection methods of related substances are constantly updated and improved. At present, the detection methods of related substances involve physical, chemical, and other fields, including chemical methods, chromatography, and spectroscopy. In this paper, the research progress of detection methods for related substances in drugs in recent years was reviewed, and the types, features, and application scope of detection methods were summarized, providing reference for quality control of chemical synthetic drugs and traditional Chinese medicines. Therefore, this work provides new ideas for the development of more accurate and efficient detection methods.

Fixed-dose Combinations (FDCs) combine two or more medications into a single dosage form. Several benefits, including impending therapeutic efficacy, a decline in episodes of adverse drug effects, pharmacokinetic advantages, a decrease in pill burden, a reduction in the dose of individual medications, and a reduction in the emergence of drug resistance, justify their acceptance. For the treatment of increased Intraocular Pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension, an FDC eye drop formulation, including ripasudil hydrochloride hydrate (0.4%W/V) and timolol maleate (0.5%W/V) has just received approval. No analytical method has been reported thus far for this newly approved combination. Thus, this review collected and simplified information on reported analytical techniques and physicochemical and biological properties for the above-cited FDCs. The authors have explored various authenticated scientific journals and presented simplified information to meet the objectives. In this study, the reported methods are spectroscopy (nil, 23%), HPTLC (nil, 10%), HPLC (100%, 61%), hyphenated techniques (nil, 6%) and electrophoresis methods (nil, 6%) for ripasudil hydrochloride hydrate and timolol maleate, respectively. Analysts using such comprehensive data might develop a method for analyzing the recently approved FDCs.

Background: Impurities may reduce antibacterial activity and affect clinical efficacy, However, there has been no report on the impurity of clorprenaline and bromhexine capsules. Objective: In order to determine the impurities in compound clorprenaline and bromhexine capsules. Methods: A new stability-indicating HPLC method was established. A Boston Green ODS column was used, and the UV detection was 225nm. Results: The established method was highly specific, sensitive, accurate, and suitable for routine quality control of clorprenaline and bromhexine capsules. The structures of unknown impurities were characterized by the MS/MS data. Conclusion: These results provide a sufficient basis for our subsequent study on the safety of Compound Clorprenaline and Bromhexine Capsules and also provide ideas for the impurity research of other compound preparations.

Background: Atopic dermatitis (AD) is an allergic skin disease that can be inherited. Crisaborole is a specific drug developed to deal with this disease. The compounds of 4-(4- Bromo-3-formyl-phenoxy)-benzonitrile and 4-(4-(4-bromo-3-formylphenoxy)-3- formylphenoxy) benzonitrile are the representative impurities in the synthesis of Crisaborole active pharmaceutical in gradient (API). Owing to the genotoxic impurities that could lead to cancer and gene mutations, it is necessary to develop a simple, efficient, sensitive, and accurate method to detect these impurities. In this study, the 4-(4-Bromo-3-formyl-phenoxy)-benzonitrile and 4-(4-(4- bromo-3-formylphenoxy)-3-formylphenoxy)benzo- nitrile present in Crisaborole API were detected using UPLC-MS/MS. Methods: The separation was made on a ZORBAX Eclipse XDB-Pheny column (4.6 mm ×75mm, 3.5 μm) with the mobile phase of acetonitrile solution containing 0.1% trifluoroacetic acid (A) and water containing 0.1% formic acid (B) in gradient elution mode. Quantification was performed using positive ion electrospray ionization (ESI), and the contents of two compounds were determined using the multiple reaction monitoring (MRM) modes. Results: The quantitative analytical method was fully validated with respect to linearity (r > 0.9998), sensitivity, precision, accuracy (the average recovery of two impurities was 84.1% to 90.7%), and robustness. Conclusion: Three batches of samples were detected by UPLC-MS/MS, indicating that the proposed approach was applicable for the quality evaluation of Crisaborole.