Quantitative Mass Spectrometry
Mass spectrometry combined with either gas or liquid chromatography is one of the most common method of detection for the bioanalysis of a drug or chemical in the low ng to pg/mL range. Useful across the entire development of your pharmaceutical industrial chemical or agrochemical, quantitative LC/MS/MS is the tool of choice for selective and sensitive detection of most compounds of interest. Delivering fast, accurate identification, the technique supports the critical analysis that drives decision-making and allows you to meet milestones on time.
Charles River has a long history of offering mass spectrometry testing services, employing decades of technical application and experience to tackle the toughest challenges encountered in developing, validating, and running LC/MS bioanalytical methods across all phases of drug and chemical development in a regulated environment. From small molecules to biotherapeutics, peptides, proteins, fusion proteins, monoclonal antibodies, and biomarkers, we have you covered.
Biological Sample Preparation
Sample preparation does not always get the respect it deserves. Ranging from a simple “dilute and shoot” to numerous popular techniques currently in use, a biological sample preparation technique should be carefully selected to meet the goals of the project. A strategic study design considers how to improve the specifications of method development, increase speed of analysis, and provide excellent results while complying with regulatory standards. Well executed mass spectrometry services pay close attention to assay sensitivity, duration of the assay over its lifetime, sample complexity, increased productivity and, when relevant, the use of automation for large numbers of samples.
The most common biological samples are plasma or serum for pharmacokinetics, drug clearance, and ½ life and bioavailability determination, while urine samples aid determination of compound elimination. Skilled in the principle sample extraction techniques of protein precipitation, solid phase extraction, and liquid/liquid extraction, our scientists also have experience with a wide range of others to tailor solutions as needed.
Developing robust chromatography is key to the success of a quantitative mass spectrometry bioanalytical method. The goal of the chromatographic process is to separate the analyte(s) of interest from both endogenous interferences and drug metabolites. Coelution of endogenous metabolites or other endogenous or exogenous species may cause ion suppression or ion enhancement, both which are detrimental to the development of a bioanalytical assay.
Selecting the most promising conditions requires knowledge of retention characteristics, resolution, slope of gradient, and retention profile of metabolite(s). This understanding, combined with knowledge from in vitro and animal experiments, is the foundation of informed decisions. Conferring frequently, our global network of bioanalytical scientists can pool available resources to optimize your method.
Mass Spectrometric Detection
Optimizing conditions for mass spectrometry detection of the compounds of interest requires evaluation of the MS response and development of a multiple reaction monitoring (MRM) methodology. In doing so, we ask several questions: Do the compounds need chemical modification to be detected? What is the best mode of ionization for detection, such as atmospheric pressure chemical ionization (APCI) for electrospray ionization (ESI)? What polarity provides the best response?
The process can be demanding and involve a series of iterations to reach an optimal set of conditions that maximize the necessary concentration and sensitivity for a specific assay. For this reason, companies of all sizes often outsource their mass spectrometry projects. When you need fast, fit-for-purpose assays, you can trust Charles River’s state-of-the-art facilities and scientific expertise to deliver superior mass spectrometry testing services.
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
- Liquid chromatography-high resolution mass spectrometry (LC-MS, HRMS)
- Liquid chromatography (HPLC, UHPLC) with UV, fluorescence, ELSD and radiolabelled detection*
- Gas chromatography (GC) with MS, MS/MS, FID and EC detection
- Inductively coupled plasma (ICP-OES, ICP-MS)
*Additional detections available
- Atmospheric pressure chemical ionization (APCI)
- Electrospray ionization (ESI)
- Electron impact (EI)
- Chemical ionization (CI)
- SCIEX API 6500, 5500, 5000, and 4000
- Waters Xevo® TQS
- Waters SYNAPT G2S
- Thermo Q Exactive™ Plus
- Shimadzu IT-TOF
- HPLC/UHPLC (Thermo Aria, Waters Acquity and Shimadzu Nexera) with UV, fluorescence, ELSD and radiolabelled detection*
- ICP-OES, ICP-MS, ICP-MS/MS
- Gas chromatography with MS, MS/MS, FID and EC detection
- 96-well plate robotic liquid handlers (Tecan, Hamilton Nimbus and MicroStar, Tomtec)
*Additional detections available
Very few laboratories match Charles River’s expertise in the sample preparation, chromatographic separation, and mass spectrometric detection that makes these ultrasensitive bioanalytical methods a success. With a global network of bioanalytical scientists and more than 130 mass spectrometers, we support early discovery pharmacokinetics and toxicology studies through method development, validation, and analysis of nonclinical and clinical biological samples in a good laboratory practice (GLP) environment.
Frequently Asked Questions (FAQs) for Mass Spectrometry Services
What is mass spectrometry?
The analytical laboratory technique known as mass spectrometry is used to separate components of a sample (drug, chemical, agrochemical) by their mass and electrical charge. The mass spectrometer produces a mass spectrum that plots the mass-to-charge (m/z) of compounds in a mixture and its three main parts are the ion source, mass analyzer, and the detector. As an analytical tool, it is used for both quantitative and qualitative analysis.
What are matrix effects in mass spectrometry?
Matrix effects can impact both the identification and quantification analysis of an analyte of interest. This alteration of ionization efficiency by the presence of coeluting substances can cause mass accuracy deviation and both ion suppression false negatives and positives. The two most common ways to assess matrix effects are by a post extraction addition or post column infusion method.
What are the key criteria to the development of a mass spectrometry bioanalytical method?
A highly sensitive MS/MS method for detection of compounds of interest in a biological matrix must meet the following criteria and encompass all parameters using a systematic approach to develop optimal conditions quickly and efficiently.
- Detection and quantitation limit
Charles River’s mass spectrometry services team consistently develops and validates such methods for the pharmaceutical, biotech, chemical and industrial, and agrochemical industries.