Cutting‐edge LC–MS/MS applications in clinical mass spectrometry: Focusing on analysis of drugs and metabolites

Abstract

In recent years, liquid chromatography with tandem mass spectrometry (LC-MS/MS) has become a fundamental technology in clinical practice. In Japan, the LC-MS/MS system is used in many large hospitals. It has become popular among pharmacists and laboratory technicians. LC-MS/MS has some advantages in terms of accuracy, speed, and comprehensiveness compared to conventional automated chemical testing equipment. However, LC-MS/MS is by no means a universal method, and it is necessary to understand its characteristics before using it. In the field of therapeutic drug monitoring (TDM), there is an issue with linearity in comprehensive measurement; however, ion-abundance adjustment methods, such as in-source collision-induced dissociation, have been proposed as a solution to this problem. The development of a biomarker analysis includes search, identification, and quantification, and it is necessary to select an appropriate mass spectrometric method for each step. In this paper, we review cutting-edge technologies that can expand the performance of LC-MS/MS in the clinical field and consider current issues and future prospects.

Development of a Highly Sensitive and Rapid Liquid Chromatography–Tandem Mass Spectrometric Method Using a Basic Mobile Phase Additive to Determine the Characteristics of the Urinary Metabolites for Niemann–Pick Disease Type C

“…Linearity, Calibration Curves, and Matrix Effects Generally, calibration curves for drugs that are not normally contained are generated by adding standard solutions to the sample matrix. [59][60][61][62][63] However, when analytes are endogenous compounds that are found in all participants, an alternative approach must be selected. 64) In this study, we prepared calibration curves using water as a surrogate matrix based on previous methods.…”

“…[1][2][3] Because disease prognosis is considered to be better when treatment begins earlier, 10) early diagnosis is desired. Biomarkers [11][12][13] that can more easily diagnose NPC are attracting attention owing to the rarity of a specialist for this disease and the complexity of the conventional methods. 7) Since 2010, oxysterols, 14,15) lysosphingomyelin, 16) N-palmitoyl-O-phosphocholine-serine [17][18][19][20] (previously called Lyso-SM-509), and abnormal bile acids [21][22][23][24] have been reported as NPC biomarkers in the blood.…”

“…Sulfated cholesterol metabolites have been reported as NPC biomarker candidates in urine. [11][12][13][24][25][26][27][28][29][30][31][32][33][34] Various conjugated cholesterols are known to be present in urine, [35][36][37] and differ-ent molecules have been detected using metabolome analysis. 27) Previously, our research group found that five urinary sulfated cholesterol metabolites are good biomarker candidates for NPC (Supplelmentary Fig.…”

Metabolite Identification of Isopropoxy Benzene Guanidine in Rat Liver Microsomes by Using UHPLC-Q-TOF-MS/MS

“…Liver microsomes make up a common in vitro system for evaluating drug metabolism profiles [ 21 , 22 ]. Liquid chromatography/tandem mass spectrometry has become a good option for the identification and structural characterization of metabolites due to its selectivity, sensitivity, and fast analytical speed [ 23 , 24 ]. Mass spectrometry is also widely used to detect and identify drug metabolites in vitro and in vivo [ 25 , 26 ].…”

A Comprehensive Study to Identify Major Metabolites of an Amoxicillin–Sulbactam Hybrid Molecule in Rats and Its Metabolic Pathway Using UPLC-Q-TOF-MS/MS

“…With the advent of liquid chromatography–mass spectrometry (LC–MS), metabolites can be fully separated, and even trace substances can be detected. Accordingly, LC–MS-based methods have become the most effective and widely used analytical tools for the identification of drug metabolites [ 27 , 28 ].…”