Rapid LC-MS/MS Evaluation of Collagen and Elastin Crosslinks in Human and Mouse Lung Tissue with a Novel Bioanalytical Surrogate Matrix Approach.

Alterations to post-translational crosslinking modifications in the extracellular matrix (ECM) are known to drive the pathogenesis of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Thus, the methodology for measuring crosslinking dynamics is valuable for understanding disease progression. The existing crosslinking analysis sample preparation and liquid chromatography tandem mass spectrometry (LC-MS/MS) methods are typically labor-intensive and time-consuming which limits throughput.

High throughput bioanalysis of serum 7a-hydroxy-4-cholesten-3-one (C4) using LC-MS/MS: Devising an end-to-end single vial solution for a sample limited application.

Crohn's disease (CD) is characterized by chronic ileal/ileocolonic inflammation, and in some cases, can result in bile acid malabsorption (BAM) and subsequent bile acid diarrhea (BAD). Although BAD is common in CD, diagnosis is difficult. In patients with CD who had ileal resection (IR), elevated serum 7a-hydroxy-4-cholesten-3-one (C4), a cholesterol-derived stable intermediate in bile acid synthesis, is associated with diarrhea attributable to BAM and therefore, may have diagnostic utility.

Signature peptide selection workflow for biomarker quantification using LC-MS-based targeted proteomics.

In contrast to quantification of biotherapeutics, endogenous protein biomarker and target quantification using LC-MS based targeted proteomics can require a much more stringent and time-consuming tryptic signature peptide selection for each specific application. While some general criteria exist, there are no tools currently available in the public domain to predict the ionization efficiency for a given signature peptide candidate. Lack of knowledge of the ionization efficiencies forces investigators to choose peptides blindly, thus hindering method development for low abundant protein quantification.

Integrity and efficiency: AbbVie's journey of building an integrated nonregulated bioanalytical laboratory.

While bioanalytical outsourcing is widely adopted in the pharmaceutical industry, AbbVie is one of the few large biopharmaceutical companies having an internal bioanalytical unit to support nearly all its drug metabolism and pharmacokinetic studies. This article highlights our experience and perspective in building an integrated and centralized laboratory to provide early discovery and preclinical-stage bioanalytical support with high operational efficiency, cost-effectiveness and data integrity. The advantages of in-house nonregulated bioanalytical support include better control of data quality, faster turnaround times, real-time knowledge sharing and troubleshooting, and lower near- and long-term costs.

Comparison of three parallelism assessment methods of biomarker quantification by LC-MS/MS: a case study of the bioanalysis of creatinine in human urine samples.

Currently, no regulatory guidelines are available for parallelism assessment for LC-MS biomarker quantification. Spike recovery, standard addition and dilutional linearity are recommended with no mention of the implications of applying these approaches. Here, using human urine creatinine, the authors compared spike recovery and standard addition in LC-MS biomarker quantification, and evaluated a new hybrid approach: parallelism QCs.