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5-(4’-(azidomethyl)-[1,1’-biphenyl]-2yl)-1H-tetrazole (AZBT) is a known impurity found in sartan medications and there is some concern that AZBT could act as a mutagen. Here, an assay has been developed for the sensitive detection of the AZBT impurity in an irbesartan drug substance and a candesartan drug product using the QTRAP 4500 system. Excellent sensitivity was achieved with lower limits of quantification of 0.5 ng/mL which is well below the threshold of toxicological concern (TTC) for these drugs. With a total run time of 8 minutes, this robust method provides require sensitivity, linearity and recovery for assessing levels in APIs and drug products.

A method for rapid quantification of TMAO, betaine, L-carnitine, acetyl-carnitine, and choline in plasma has been developed on the QTRAP 4500MD system. This method has the advantages of high specificity, linearity, and high accuracy. As shown, this method is suitable to support rapid monitoring of TMAO metabolites: • Rapid 5.5-minute run time provided good peak separation for detection in a shorter run time than several recently published methods for faster screening. • Consistent quantification results were obtained for all standards tested, with correlation coefficients ranging from 0.991 to 0.999 • Inter- and intra-day reproducibility and accuracy meet standard bioanalytical requirements of %CV less than ≤ 15% in for all analytes analyzed in plasma • Method was evaluated in plasma matrix using a simple extraction protocol and good signal/noise was observed.

In many laboratories across the world, acylcarnitines and related molecules from a variety of sample types are quantified to investigate metabolic conditions, such as organic acidemias and fatty acid oxidation defects. Carnitines and acylcarnitines vary in their hydrophobicity, ranging from small, polar carnitine to acylcarnitines with very long acyl chain lengths. This variability poses a unique challenge for chromatographic method development. This assay is performed without derivatization and with minimal sample preparation to quantify these low-level analytes in a biological matrix.

Nitrosamine analysis has recently become one of the largest areas of interest in the pharmaceutical industry after their production in numerous active pharmaceutical ingredients (APIs) and drug products was found to be possible. Because nitrosamines are believed to be genotoxic, their strict regulation is necessary to ensure human health is not adversely affected. Here, methods have been provided that aim to improve upon the recently released European pharmacopeia chapter 2.5.42, N-nitrosamines in active substances, by optimizing run time, expanding the number of nitrosamine compounds analyzed, and increasing sensitivity.

In order to increase the safety and efficacy of drug products, impurity profiling is routinely performed to identify and quantify any residual impurities. In this study, the X500R QTOF system coupled to a ExionLC™ UPLC system with photodiode array detection (PDA), SCIEX OS Analytics, and MetabolitePilot™ 2.0 software were used to measure stability and detect impurities in amiodarone samples. This integrated hardware and software solution compounds from MS and MS/MS data and reduces the need for manual review.

Since 2018, there has been high concern about the presence of nitrosamine impurities in certain drug products. More recently concerns have been raised about the potential presence of NDMA in pioglitazone manufactured in India. Here a method has been developed using the X500 QTOF system for the detection of six nitrosamines in pioglitazone. Good chromatographic separation of the drug product from the impurities was achieved. Using both MS and MS/MS data, good sensitivity was observed for detection below the required limit of 30 µg/g. Concentration curves showed good linearity across the range tested.

Nitrosamine analysis has recently become one of the largest areas of interest in the pharmaceutical industry after their production in numerous active pharmaceutical ingredients (APIs) and drug products was found to be possible. Because nitrosamines are believed to be genotoxic, their strict regulation is necessary to ensure human health is not adversely affected. Here, methods have been provided that aim to improve upon the recently released European pharmacopeia chapter 2.5.42, N-nitrosamines in active substances, by optimizing run time, expanding the number of nitrosamine compounds analyzed, and increasing sensitivity.

Genotoxic impurities (GTI’s) are intermediate reactive products or degradants formed during drug synthesis formulation or storage. These impurities can damage human genetic material at very low levels, leading to DNA mutations which can contribute to tumorigenesis and carcinogenicity. In this publication, a method for the analysis of eight nitrosamine compounds is described.

Oligonucleotide therapeutics and gene therapies are rapidly gaining attention as their potency improves and delivery challenges are addressed. Liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) is an attractive technique for the analysis of oligonucleotide therapeutics.

With biopharmaceuticals in development showing a high level of diversity, there is the need for a high degree of flexibility for analytical methods being used to quantify these molecules. Bioanalysis of larger protein-based therapeutics is widely focusing on the enzymatic digestion of the protein, followed by the quantification of surrogate peptides on MS or MS/MS level.