The process of analytical method development begins early in drug discovery and evolves in terms of needs and goals as a candidate approaches final release. Initial method development done to determine racemic content or quickly separate major impurities is honed as compounds become fewer in number and the focus shifts to making robust and repeatable analyses. As a candidate moves from early stage development toward formulation and stability concerns, the need for continuing method development persists and the challenges of separating related or interfering compounds increases. The power of sophisticated chromatography and detection techniques, such as comprehensive multi-dimensional liquid chromatography (LC) and time-of-flight mass spectrometry (TOF-MS), can be employed to the challenges of advanced method development

To meet these needs, Shimadzu offers a variety of solutions including chromatographic method development platforms, TOF and quadrupole mass spectrometry, a full suite of molecular spectroscopy equipment, and powerful software tools based on LabSolutions. With workflows to support photo diode array peak deconvolution, impurities discovery, and LC method transfer, we give you insight to catch coeluting impurities even without separation and move methods from system to system. Add in compliance-enabled integration across multiple instrument types including balances, physical testing, LC, GC, LC-MS, GC-MS, ICP-OES, ICP-MS, FTIR, UV, Fluorometry, and TOC, to see how Shimadzu and LabSolutions can help you create efficient and robust analytical methods that move from development to QA/QC with ease.

Featured Solutions & Applications

Method Scouting Solution for UHPLC/HPLC/SFC


Method Scouting System is a method development system based on Shimadzu’s UHPLC technology. The combination with Method Scouting Solution dedicated control software achieves a fast and accurate method scouting workflow, offering excellent support for method development.

Structural analysis of impurities in pharmaceutical ingredients using trap-free 2D-LC high-resolution accurate mass spectrometry


High performance liquid chromatography (HPLC) is the primary means for impurity testing in pharmacopeia. Solutions containing non-volatile salts are frequently used as a mobile phase because of the irreplaceable advantage to achieve better chromatographic performances. However, non-volatile mobile phases are not compatible with mass spectrometry which is commonly used for structural analysis of impurities. Trap-free two-dimensional HPLC (trap-free 2D-LC) can fill this gap by exchanging a non-volatile mobile phase with a volatile one compatible for mass spectrometry. In this study, we demonstrate how structural analysis of impurities in pharmaceutical ingredients is feasible by using trap-free 2D-LC coupled to quadrupole time-of-flight mass spectrometry (Q-TOF MS) without modifying the original method mobile phases.

Simplified approach for structural elucidation and quantitation for pharmaceutical API and related impurities


Various guidelines require the impurities of drug substance and drug product be structurally identified and quantitated based on dosage. Source of these impurities could be innumerable based on raw material, process, product, packaging etc. In this study, a workflow is demonstrated (Figure 1) for
deducing probable structure of Paracetamol related impurities using Shimadzu LCMS-9030 and Insight Explore software.

Improved Analytical Workflow for Phospholipids by Nexera-e and Co-Sense for Impurities


Smart Metabolites Database registers MRM information of 475 metabolites mainly contained in biological samples such as blood, urine and cells. It enables simultaneous measurement of 475 metabolites using MRM mode. This application data sheet presents an analysis of metabolites in standard human plasma using the scan and MRM methods included in the Smart Metabolites Database, as well as a comparison of the results.

Isolation and identification of Atorvastatin degradation impurities by UFPLC


Atorvastatin is an antilipemic drug belonging to the statins class, whose reference drug is Pfizer’s Lipitor. It is used to reduce the levels of lipoproteins rich in cholesterol and reduce the risk of coronary artery disease. The drug in question is commonly sought after by pharmaceutical industries that produce generic drugs, due to the fact that the drug has a high value price, it is consumed globally, and its patent expired in late 2010. Atorvastatin has been found to degrade under acid and basic conditions. Prominence UFPLC, Ultra Fast Preparative and Purification Liquid Chromatograph, which enables fast recovery of highly purified target compounds from complex samples such as organic synthesis reaction mixtures and natural products. Prep LC is a widely used technique in many research development and manufacturing applications, including the synthesis of new drug compounds, the discovery of active components in natural products, and as a mechanism to collect large amounts of unknown compounds in foods and drugs for subsequent structural analysis.

Isolation and identification of Fluticasone degradation impurities by UFPLC


The Prominence UFPLC seamlessly integrates traditional Prep LC with novel fraction trapping for upto five compounds of interest. The instrument is controlled by a dedicated walk-up software designed to empower nonexpert users to easily set conditions for chromatographic separation and isolation of target compounds, trapping, purifying, eluting and collecting highly purified compounds in as little as 90 minutes. For applications involving the isolation of low concentration targets, replicate injection and collection to the same trapping column to increase the amount of compound trapped on column prior to elution is easily accomplished.

Method Transfer and High-Speed Analysis of Impurities of Drug by Prominence-i


Here, using the new Prominence-i integrated high-performance liquid chromatograph, we conducted analysis of substances chemically related to bepotastine besilate in accordance with the Japanese Pharmacopeia, while at the same time comparing the analysis results between those using the Prominence-i and those obtained using both the conventional integrated lC-2010 model as well as a third-party company's LC system. In addition, we introduce an example of method transfer from that used with Shimadzu's conventional system or that of a third-party LC system, respectively. At the same time, we introduce an example of high-speed analysis using the Prominence-i in which the analysis time is shortened to about one-fourth the time, while conforming to the Japanese Pharmacopoeia default of conditions.

Improvement of Quantitative Performance for Ibuprofen Using UV Cut-Off Filter on SPD-M40


Ibuprofen is an example of a nonsteroidal anti-inflammatory drug (NSAID) and is widely used as an antipyretic or analgesic agent. It has been reported that during tests to confirm stability during storage, decomposition products were generated due to temperature, acidity, light irradiation, etc. of the surroundings. In particular, the area percentage of 4-isobutylacetophenone, one of the decomposition products, increased by about 40% after the 72-hour light irradiation test. The Nexera Series photodiode array detector SPD-M40 is equipped with a UV cut-off filter that exlcudes light in the ultraviolet range, in order to ensure more stable detection of compounds that are prone to photodegradation. We are introducing examples of improving the quantitation of ibuprofen using the UV cut-off filter function of the SPD-M40.

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