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20+ Years Of Bioanalysis
600+ Small/Large Molecule Studies
400+ Custom Bioanalytical Assays
200+ Investigational Drugs
1,000+ Biomarker & Cytokine Assays

Which LCMS Testing Lab Mass Spectrometry Services Do We Offer?

Advanced Mass Spectrometry Services For LCMS Assay Development, Troubleshooting, And GLP LC MS MS Analysis To Accelerate Your Pharmacokinetic (PK), Toxicology (Tox), Biomarker, Bioavailability (BA), Bioequivalence (BE), DMPK/ ADME, LCMS Drug Testing And Other Research Studies!

LC MS Method Development, Optimization, Or Method Transfer

  • First Time LC MS Method Deveopment or LC MS Method Transfer for sensitive, selective, and specific PK/Biomarker Assay
  • Protein Precipitation (PPT), Liquid-Liquid Extraction (LLE), Solid Phase Extraction (SPE) Sample Preparation for LC MS MS Analysis of Small Molecules, Peptides, mAbs, Oligonucleotides, etc

GLP LC MS/MS Method Validation Services And LCMS Sample Collection Recommendation

  • Full or Partial LC MS Method Validation as per ICH/EMA/FDA Bioanalytical Assay Validation Guidance (GLP, GCLP) in the Context-of-Use (COU)
  • Highly sensitive, validated LC MS Assay with broad dynamic range given usual clinical sample collection and storage limitations

LC MS Services For Preclinical Animal Studies Or Clinical Drug Monitoring

  • LC MS Services for GLP PK, Tox, Bioavailability, Bioequivalence studies in rodents and large animals as well as analysis of samples in clinical studies
  • LC MS Lab for Pharmacokinetics evaluation in multiple matrices including plasma/serum, urine, CSF, stool, cell lysates, and tissue homogenates

Combined LC MS/MS Analysis For Multi-Analyte Drug or Biomarker Assays

  • LC MS Assay CRO services to quantitate Drug-Drug Interaction Or drug, prodrug, metabolite in a small sample
  • LC MS Lab to detect multiple biomarkers simultaneously (or as single analyte) at Picogram/mL concentrations

Miscellaneous Preclinical and Clinical Custom LCMS Lab Analysis Support Services

  • Tailored LC MS Lab DMPK/ ADME research services using proprietary or commercial assay supplies
  • Documentation and Reports covering LC MS Assay objectives, methods, analysis, and results for bioanalysis in a variety of species and biological matrices

LCMS Testing Lab Services For Long Term Storage Stability And Discovery Assay

  • Qualifying your Therapeutic’s Formulation, PK, or Biomarker Sample analysis for long term storage
  • Reporting Formulation, PK, or Biomarker Method Set-up and Test run(s) for stock solutions, calibration curve, and quality control samples

Benefit From Our Deep Expertise In LC MS Method Development And Validation For Your Mass Spectrometry Lab Services!

Get In Touch With Us Today For Your LC MS Analysis And Discuss Any Of Our Relevant Case Studies Below:

  • Peptide With Warhead: PK LC–MS/MS Method Development And Validation In Rat, NHP, And Human Plasma
  • Oncology Drug: Combined LC-MS PK Method Development And GLP Validation For Drug, Prodrug, And Metabolite In Rat And Dog Plasma
  • Tetrahydrocannabinol (THC), Melatonin, And Metabolites: Combined PK Method Development And LC-MS/MS Validation In Human Plasma
  • DNA Adducts: LC-MS/MS Method Development, Qualification, And Sample Analysis In Ex-Vitro Cell Lysate Samples
  • Antisense Oligonucleotide (ASO): LC–MS/MS Method Transfer And FFP Qualification In Rat And NHP Tissue Homogenates/Lysates
  • 21 Amino Acids: Combined LC-MS/MS Biomarker Method Development And Validation In Human Plasma
  • Cardiovascular Device: LC MS Method Development And Validation In Porcine Whole Blood And Nine Different Tissue Homogenates/Extracts
  • Free Fatty Acids: LC-MS/MS Method Setup And LCMS Sample Analysis Of Fourteen (14) Free Fatty Acids (FFA) And Deuterated Fatty Acids

Tackle Your LC-MS Assay With Our Mass Spec Company Now!

Our Team Has Delivered LC MS MS Service In 400+ Bioanalytical Studies Over 20+ Years To Support Our Visionary Biotech And Pharma Sponsors!

20+

Years of Bioanalysis Services in Industry Leading Time

400+

Custom Bioanalytical Methods Completed Within Budget

Comprehensive LC MS MS Services For PK, Tox, Bioavailability, And Biomarker To Exceed Your Expectations

  • Your LC MS Assays matter to us. Don’t allow any novice LC MS laboratory CRO to gloss over hidden pitfalls that can delay the development of your next therapeutic.
  • You need to make a difference to patients. Having an extremely responsive and flexible LC MS Services Assay Lab at your disposition will tremendously expedite your drug development.
  • Your bioanalytical budget is limited. Our LC MS Method Development expertise will ensure that quickly get farther along the regulatory submission process without unnecessarily spending more.

Do not wait any longer.

Expected Services Turnaround

We whole-heartedly cooperate with your team to accomplish our shared goals and accelerate your LC MS PK/Biomarker study timeline. For example, we need just two-to-three weeks for LS-MS/MS assay development and validation. Afterward, we need a couple of weeks for submitting your audited report with complete details of validation experiments. Here, we pull together our core strengths – scientific experience, regulatory expertise, and operational excellence – to make sure your resources and costs are optimized.

Requested Sponsor Input

Our team thrives on open lines of communication between sponsors and our frontline scientists, project managers, quality assurance unit, lab staff, etc. Could you please share additional details about your analyte(s), preferred critical reagents and LC MS assay supplies, current LC MS assay (s) with chromatography and mass spectrometer conditions, data from previous assay run(s), study protocols (with # of cohorts, samples), etc to expedite outlining the scope of work for quotation and timeline estimation?

Sponsors Love Our LC MS Laboratory Mass Spectrometry Testing Services For Top Quality And Industry Leading Turnaround

Connect With Us for a Reference Call with Them!

NorthEast BioLab truly goes that extra mile, and we hope to continue enjoying seminal interactions with them.

NorthEast BioLab presents a science-based, hands-on, no-frills approach on the latest bioanalytical platforms.

NorthEast BioLab is by far the most responsive and thorough bioanalysis lab services CRO.

As a small company, our vendors are key members of our project teams. The scientists at NorthEast BioLab are technical experts, who produce high-quality data, on-time, and on-budget.

We partnered on several programs and found NorthEast BioLab responsive, collaborative, and reliable.

We trust NorthEast BioLab to design and execute the most streamlined and impactful bioanalytical projects.

We found their integrity as refreshing as readiness to provide creative scientific input and high-quality data.

We have worked with NorthEast BioLab for over ten years given their commitment to highest quality bioanalytical data.

NorthEast BioLab tremendously supported us in reproducing our critical lab discoveries for drug metabolism.

NorthEast BioLab always exceeds expectations on bioanalytical assay development, validation, and sample analysis.

We are thrilled to complete our bioanalytical studies with their top quality and incredibly responsive team.

We worked closely to implement the most efficient and cost-effective bioanalytical assay for our PK Studies.

Our projects with NorthEast BioLab include successful method development, validation, stability studies during Clinical Phase I – IV studies.

NorthEast BioLab provides critical insight, and are compliant with regulatory standards and industry best practices. We highly recommend them and look forward to working together again.

Our latest successful study was a pivotal bioequivalence study, where samples from a cross-over study with about 100 volunteers needed swift analysis.

This study, same as all other bioanalytical studies with NorthEast BioLab, was completed with top quality and reporting standard with incredible responsiveness.

Don’t Wait, Start Your Crucial Mass Spec LC MS Services Today!

Efficiently Accelerate Your PK, Tox, Bioavailability, And Biomarker LC-MS/MS Analysis With Our Veteran Bioanalytical Experts

Expert LC MS Assay Mass Spectrometry Services

  • Extensive LCMS Bioanalysis and Mass Spectrometry Assay Expertise with a deep bench of veteran scientists to get it right in first go
  • Upfront review of your LC-MS/MS method(s), current data, regulatory/sponsor requirements, assay supplies, etc.
  • Regulatory awareness for GLP LC MS Method Validation – 30+ years relationship within life sciences community

Tailored Mass Spectrometry Assay Lab And LC MS MS Service

  • Responsive LCMS Bioanalysis Services CRO focused on Turnaround, Flexibility, Transparency, and Feedback
  • Open Communication between Senior Scientists and Sponsors on all potential LCMS sample preparation and LC MS/MS Assay troubleshooting approaches
  • Program Continuity and Quality Assurance with 100% focus on your LC MS Assay and LCMS Sample Analysis

Complete Guide On LC-MS: Working, Analysis & Methods

Mass spectrometry Assay is a widely used procedure observed as having outstanding sensitivity. Triple-quadrupole mass spectrometry (MS/MS) offers additional benefits due to its selectivity. In mass spectrometry analysis, it is essential to isolate….

Our Streamlined Process For On-Time Delivery Of Entire Scope Of Work Within Sponsor Budget

Trust Our Mass Spec Company For Your LC-MS Assay Quantification.

What Makes Us The Best Choice For Your LC-MS Analysis And Mass Spectrometry Lab Services?

We Are A Trustworthy LC-MS Method And Mass Spectrometry Lab With Over Two Decades Of Hands-On Experience With Hundreds Of Novel And Approved Drugs!

  • Tailor-Made, High-Value LC-MS Lab Services For Small Molecules, Peptides, mAbs, Oligonucleotides, Etc. In Diverse Matrices
  • Preclinical/Clinical LC-MS Assay Using Proprietary or Commercial Reference Compounds And Internal Standards
  • On-going LC-MS Analysis Services For Drug Compound Screening And Improvement During Early Discovery
  • LC-MS Method Development And Validation As Per FDA BMV Guidance For Chromatographic Assay (CC)

Contact A Scientist With Your LC-MS/MS Analysis Assay Details

We Will Respond Within 1 Business Day

Support Your Drug Innovation With Entire Suite Of LCMS Bioanalysis Services In Safe Hands Of Our Veteran Scientists

We Judiciously Invest In Our People, Solutions And Infrastructure, And Regularly Review Our Business Processes And Practices To Exceed Sponsor Expectations

How Can Our LC MS Lab Services, Mass Spec Lab CRO Benefit You?

Related FAQs

Answers to additional Liquid Chromatography
Mass Spectrometry (LC-MS) Analysis Lab Services questions popular among our potential sponsors.

What Is LC-MS Analysis?

LC-MS Analysis: Robust and Reproducible Bioanalytical Assay with High Throughput and Sensitivity

Liquid Chromatography Mass Spectrometry (LC-MS) is a method or technique used commonly for drug analysis, food analysis, and environmental testing. The advantage of LC-MS analysis is that it enables both high throughput and high sensitivity analysis of analytes. LC-MS assay is increasingly used for a variety of compounds leading to accelerated testing and development of drug candidates. Similarly, LC-MS analysis is one of the most commonly used techniques for conducting DMPK studies. Liquid Chromatography Mass Spectrometry combines the physical separation and detection sensitivity capabilities of both platforms.

In other words, the individual abilities of both the LC and MS techniques are synergistically enhanced by their tandem combination. LC-MS analysis works so well because the Liquid Chromatography separates analyte from a complex matrix into distinct components, while the Mass Spectrometry provides the characterization and quantitation for the components with high accuracy. This technique works exceptionally well for the analysis of both synthesized inorganic compounds, as well as organic and biochemical compounds found in complex biological and environmental matrices. For 20+ years, pioneering biotech/pharma companies rely on our LC-MS/MS Analysis experts to drive industry-leading value and turnaround. Our FDA audited LC-MS testing lab always generates reliable and robust data for your pivotal studies. We routinely pilot a wide variety of GLP LC-MS Method Development and Validation projects to meet your critical bioanalysis milestones.

When Is LC-MS Method And Analysis Used?

LC-MS Method Setup and Sample Analysis during Drug Development
The LC-MS assay method is used during various stages of the drug development cycle. Most notably, it is used in the following phases:

Drug Discovery:

Over the past couple of decades, high-performance liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) analysis has emerged as one the preferred analytical technique for new drug discovery assays.

Preclinical Toxicology:

Studies range from early lead optimization to dose range finding studies followed by Tox studies. These studies involve primarily plasma and tissue samples of rodent and non-rodent species.
Typically, GLP toxicology studies are performed using fully validated LC-MS methods. Theoretically, this could be accomplished using HPLC with UV and other detection methods like fluorescence, but these detection methods aren’t as selective and require extensive sample preparation. Use of MS detection in multiple reaction monitoring mode (MRM) is quite selective, and therefore drugs can be analyzed in biological matrices with simple cleanup steps. Also, LC-MS assay can be developed relatively faster for a new drug and are generally very robust and reliable.

Clinical trials:

These studies range from Phase 1 (dose escalation studies like single ascending and multiple ascending dose, healthy volunteer studies) to Phase III, Phase IV and post-marketing studies. Matrices involved in the analysis range from plasma, serum, blood, urine, feces, and tissues from different organs.
Over the last 10-15 years, the LC-MS/MS method has rapidly become the method of choice during clinical trials. At the early stages of clinical development, it is essential to analyze plasma samples from clinical trials for understanding ADME properties of the drug and ensuring data consistency with preclinical PK studies. Thus, LC-MS/MS methods are developed and validated for the drug analysis and testing in human biological fluids.

Liquid Chromatography:

Here’s how the entire LC-MS assay works:
As the first step, the liquid chromatography is used to separate the proteins, nucleic acids, or other endogenous material in complex biological matrices. There are only minor differences between HPLC (High-Performance Liquid Chromatography) setup with other detectors compared to how HPLC-MS is set up. Among other aspects, these differences include the column length and flow rate. Benefiting from the mass spectrometer, chromatography columns used in LC-MS/MS tests are much shorter than those used in standard HPLC. For example, the regular columns are about 100-300 mm long while those in the LC-MS method are only about 30-50 mm long. Consequentially, the flow rate for LC-MS is slower than the flow rate in the HPLC technique which is 1ml/min. Since the LC-MS combines the advantages of HPLC with mass spectrometry, it can be used for a wider variety of drug analysis as well as environmental testing and food analysis.

Mass Spectrometry:

The instrument consists of three major components:

  • Ion Source: Produces gaseous ions from the substance being analyzed.
  • Analyzer: Resolves the ions into their mass components according to their mass-to-charge ratio.
  • Detector System: Detects the ions and record relative abundance of each of the resolved ionic species.

First step in the mass spectrometric analysis is the production of gas phase ions of the compound by electron ionization. The molecules that come out of the chromatography column are highly pressurized. Since the mass spec units operate in a vacuum, the continuous flow cannot be detected by the spectrometer. Therefore, the liquid eluted from the chromatography column must be passed through an interface before it can be transferred to the mass spectrometer. The most common interfaces are atmospheric pressure photo-ionization (APPI) systems, atmospheric pressure chemical ionization (APCI) systems, and electrospray ionization (ESI) systems. The liquid that passes through the interface gets nebulized into a spray, after which it is ionized and transferred to the mass spectrometer.
The mass spectrometer measures the mass-to-charge ratio of the ions and then records the relative abundance of each ion type, producing a mass spectrum of the molecule. The equipment displays results in the form of a plot of ion abundance versus mass-to-charge ratio.

How do you perform LC-MS Method Development?

We have 15+ years of experience in performing robust LC-MS method development using appropriate chromatography column and mass spectrometer system settings. Generally, it takes a few iterations to achieve desired LC-MS method parameters before finalizing an effective assay. We must optimize these numerous LC-MS method development parameters, such as ionization mode, parent and fragment transition ion pairs, polarity, and source parameters including gas flows and temperature, to detect and quantitate a chosen compound successfully. First, we must determine how the test article ionizes when developing a mass spectrometry method. Electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI) are two of the most widely used methods that can be run in both positive or negative polarities. Our team identifies the selection of proper ionization mode as critical and usually the first condition to be determined. If no prior references in literature are available, our experienced scientists can make an educated and informed guess about initial conditions based on your drug compound details (structure, molecular weight, etc.). Otherwise, we choose an ionization mode and polarity by testing different ionization probes in both positive and negative polarities to determine the ideal starting approach. Next, our scientists evaluate the MS response and create a methodology that provides the best MS conditions for detecting your compound. Thus, we select the most reliable ionization potential and obtain the most suitable m/z value (parent or daughter ion) for optimal sensitivity and selectivity. Ideally, we could see our analyte(s) of interest distinctly from all endogenous interferences and drug metabolites using robust chromatography and the superior selectivity of MS/MS detection. Typically, the most commonly adjusted factors for LC system setup are mobile phase, stationary phase, or column, chemistry, gradient, flow rate, and column temperature with development tailored to intended use inclusive of method development time, analysis run-time, expected number of samples per day, and analytical concentration range. For the liquid chromatography development, one of the first steps during the LC-MS/MS method development is determining the retention characteristics of the compound(s) of interest. With biological matrices, it is often critical to ensure that test compounds elute away from the solvent front where interference from endogenous sample components can occur. Often, we can quickly solve this puzzle by screening at low and high pH using a simple reversed-phase gradient and a high retention column such as C18, or other suitable stationary phases dependent upon the test article chemistry. Notably, proper sample preparation for LC-MS analysis is critical for ensuring that our assays meet recommended compliance and performance standards. Ultimately, we understand that analytical performance is dependent on a clean and stable sample, yielding method robustness, reliability, and reproducibility.

Why Choose Us For Your LC-MS Method And Analysis Assay?

Reliable Bioanalytical Lab With 20+ Years Experience In Hundreds of LC-MS Method and Analysis Assay for Various Novel/Approved Drugs

We use state-of-the-art techniques when it comes to method development and sample analysis. Liquid Chromatography-Mass Spectrometry is one such technology that has become increasingly popular in recent years because it combines the capabilities of two different techniques in a very synergistic manner.

For LC-MS bioanalysis, your partner needs to offer the right experience and expertise. Given how time-consuming and painstaking drug development process can be, you need a partner that’s willing to go that extra mile. At NorthEast BioLab, we combine 15+ years of experience in LC-MS method development and validation with deep client empathy to offer a wide variety of drug discovery and development studies.

Finally, we whole-heartedly cooperate with you to accomplish our shared goals and accelerate your study timeline. Our team always keep the lines of communication open between our clients and frontline managers and lab staff. We bring together our core strengths- operational excellence, regulatory expertise, and scientific experience, to make sure your costs and resources are optimized.

What types of analytes can be quantitated with LC-MS assays?

LC-MS assay offers a sensitive, selective, and reliable approach for analyzing diverse molecules. Different mass spectrometer models provide advantages and disadvantages for viable LC-MS analysis over mass ranges and detection limits. Most biomolecules utilized as reference materials for drugs, metabolites, or endogenous biomarkers, including drugs, peptides, nucleic acids, and other endogenous or synthesized molecules, can be assayed using triple quadrupole mass spectrometry. Triple quads, however, have limited mass ranges, and intact proteins and large biomolecules can alternatively be assayed by other LC-MS testing techniques, including time-of-flight (TOF) or other high-resolution mass spectrometers (HR-MS). Inductively coupled plasma mass spectroscopy (ICP-MS) is especially useful for metallic ion assay in environmental chemistry and clinical toxicology.

What types of sample matrices can be analyzed in an LC MS testing lab?

In LC-MS lab setting, aqueous and organic solvents, dosing vehicles, or other drug formulations prepared for in vivo or in vitro testing, and biological fluids and tissues are routinely quantified for drug substances, metabolites, and biomarkers. Biological samples for LC-MS analysis may include Blood, Plasma, Serum, Tissue Homogenates/Extracts (Liver, Lung, Kidney, Brain, Tumor, Arterial, Tendon, Skin, etc.), Translucent Matrices (Urine, Cerebrospinal, Tears, Synovial, Aqueous, etc.), Cell Lysates, and several other body fluids or membranes.

How are samples prepared for LC MS testing?

For solid tissue samples, sample homogenization is typically performed as part of the sample processing for LC-MS testing. For all matrices, samples must be extracted into solvents suitable for injection for LC-MS assay. Protein precipitation (PPT), liquid-liquid extraction (LLE), and solid-phase extraction (SPE) are the most commonly used sample extraction techniques used in LC-MS labs during sample preparation for LC-MS analysis. The extraction method employed is verified during LC-MS/MS method development and method validation.

How much sample volume is needed for LC-MS assay?

In any LC-MS testing method, the required sample volume depends on multiple factors such as calibration range, compound sensitivity, chromatography column, matrix-based suppression or enhancement, mobile phase selection, and detector linearity. Often, LC-MS method sample volume requirement can vary between 2 µL-200 µL. We can use specialized systems such as capillary flow for shallow volumes. Our scientists recommend collecting additional sample volume in pharmacokinetic/toxicokinetic assessments from biological samples to complete reassay or incurred sample reanalysis (ISR) to support your LC-MS method validation.

How do you select the buffer for LC-MS assay?

Buffers and mobile phase solvents used in LC-MS applications should ideally only contain volatile components. The most common volatile salts for buffering in LC-MS mobile phases are ammonium formate and ammonium acetate. Here, adjustments in pH are performed with volatile acids and bases such as formic acid and ammonia. Usually, some non-volatile components get introduced during assays of biological samples with sample injections. Mass spectrometer instruments can handle small amounts of these non-volatile components with routine cleaning and maintenance.

How to reduce carryover in LC-MS assay?

In LC-MS assays, a mechanical region in the flow path is often the source of carryover. Most commonly, carryover occurs in the autosampler needle or chromatographic column used for the assay. Lab technicians can inject blanks during LC-MS analysis to gradually dilute the hold-up of partial samples, resulting in less carryover with each pass. Similarly, we can apply an organic solvent as a needle wash solution when analyzing hydrophobic samples to minimize carryover by solubilizing and washing away the adsorbed sample components. Here, the analyst must handle the needle wash solution in the same way as the mobile selection during the method development of LC-MS assay. Advanced instrument models allow for more solvents, higher flow rates, and other advanced washing mechanisms to help reduce autosampler-based carryover. We can minimize chromatographic carryover by sample dilution, smaller injection volumes, or changes in the stationary and mobile phases of the assay.

What’s pre-validation and test run in LC-MS analysis?

Pre-method or Test validation is a process designed to confirm that the procedure employed for a specific assay is suitable for its intended purpose ahead of actual LC-MS method validation. Test method validation provides an overall understanding of the uncertainty of the LC-MS method, stability of the analyte during storage, method processing and analysis, and reproducibility and ruggedness of the LC-MS assay. FDA and other regulatory agencies mandate full method validation for each test article, sample matrix, analyst, and LC-MS instrument system before regulated sample analysis.

Do we need to replicate samples in LC MS testing?

We can compare replicate LC-MS/MS runs using experimental duplicate to inform us on precision further and help assess whether our LC-MS method and sample analysis are performing as expected. Generally, replicate samples are analyzed on an as-needed basis for LC-MS testing due to resource constraints and relatively longer run times associated with chromatographic assays.

What are the primary elements of LC-MS method validation?

All high-Quality LC-MS method validations ensure that the analyte of interest can be detected selectively, accurately, and precisely in an appropriate calibration range suitable for sample analysis. Furthermore, these LC-MS method validations must include proper safeguards to verify all test compounds are stable during sample collection, storage, and processing. To that end, FDA guidelines on chromatographic method validation mandate demonstrating selectivity, specificity, sensitivity, accuracy, precision, recovery, and stability under storage and test conditions. Usually, a change in analyte, detection range, or sample matrix results in a shift in the method and the need for additional LC-MS method validation. Frequently, LC-MS assays are validated on any system and for any analyst performing the LC-MS method to ensure that LC-MS/MS analysis results are robust, reliable, and reproducible.

Can I adapt my LC-UV/Vis method for LC-MS method development?

For many molecules, methods for UV/Vis detection may be modified for detection by mass spectroscopy. Often, LC-MS analysis will offer an improved selectivity, sensitivity, and linear dynamic range relative to LC-UV/Vis analysis. Modifications to the method typically include switching to volatile mobile phases for compatibility with MS source introduction and selecting a more appropriate internal standard, such as a stable-labeled isotope of the analyte, for LC-MS method development and validation as well as during sample quantitation.

Are there any additional applications of LC-MS analysis beyond sample quantitation?

LC-MS analysis has extensive industrial applications beyond sample quantitation as often LC-MS analytes can be chemically, thermally, or enzymatically labile. For instance, we can perform LC-MS analysis to detect, isolate, or purify certain chemical compounds. In pharmacology and environmental settings, we can utilize LC-MS/MS to assess the stability of xenobiotics, drugs, metabolites, or toxicants in various sample matrices. Furthermore, we could use LC-MS detection for metabolic lability, structural and metabolite identification from in vitro sample incubations or in vivo pharmacology studies, and other in vitro ADME determinations such as protein binding, cell permeability, or drug-drug interaction potential. LC-MS analysis can apply to samples originating from industrial hygiene monitoring, environmental sampling, fermentation broths, growth media, the agricultural industry, process control, biomedical studies, food testing, and countless others avenues.

What types of mass spectrometers are typically used in LCMS labs?

Generally, triple-quadrupole mass spectrometers are used in analytical and bioanalytical LC-MS laboratories for quantitative small-molecule applications due to their selectivity and sensitivity advantages. Time-of-Flight (TOF) and QTrap LC-MS models are more commonly used in qualitative applications, such as metabolite or structural identification, combined with alternate analytical approaches such as nuclear magnetic resonance (NMR). Laser desorption mass spectrometers (MALDI and SELDI) can be used to analyze large molecular weight biomolecules. Inductively coupled plasma mass spectroscopy (ICP-MS) is utilized to study metallic ions, often in environmental labs and toxicology settings to diagnose heavy metal or radioisotope exposure.

Is there a difference between LC-MS and LC-MS/MS?

The terms LC-MS and LC-MS/MS are often used interchangeably. Technically, LC-MS refers to a single quadrupole system with only one mass filtering quadrupole, while LC-MS/MS indicates a triple-quadrupole system with two mass filtering quadrupoles. In LC-MS/MS system, Q1 and Q3 quadrupoles function as mass filters and Q2 acts as a collision cell to generate product ions. Typically, LC-MS is more sensitive, but the improved LC-MS/MS selectivity allows for cleaner, more reliable analyses from complex matrices. LC-MS analysis of low molecular weight compounds requires a clean sample matrix to avoid the interference of unwanted ions. We can assay these compounds more efficiently using triple-quadrupole mass spectroscopy, allowing lowered noise, higher selectivity, and increased linear range.

What are the advantages and disadvantages of LC-MS analysis?

LC-MS analysis offers a sensitive, selective, and moderate-to-high throughput technique for sample quantitation of drugs, metabolites, and biomarkers in samples from various analytical and biological matrices. Different instrument models and detection techniques like ion traps and time of flight mass spectrometers provide valuable tools for qualitative structural identification and drug metabolism studies. LC-MS has historically had limited application for quantitation of intact biomolecules, even as some newer instrument models offer high mass detection. LC-MS lab systems are costly to implement and maintain, require skilled operators for method development, regular instrument calibration and troubleshooting, and provide low throughput for LC-MS sample analysis. That said, clinical laboratories during the last 15 years have experienced an enormous increase in the use of liquid chromatography-tandem mass spectrometry (LS-MS/MS). Newborn Biochemical Genetics and Drug/Toxicology Endocrine laboratories have surpassed screening laboratories as the leading clinical LC-MS/MS users. LC-MS methods now measure most steroids and biogenic amines in US reference/referral laboratories, and the technique is beginning to spread to smaller labs.

What are the limitations of the LC-MS Platform?

LC-MS/MS platform offers higher throughput than gas chromatography-mass spectrometry (GC-MS) and analytical specificity superior or comparable to immunoassays. However, LC-MS/MS has numerous limitations, most of which revolve around the interacting triangle of sensitivity, specificity, and throughput. While sample throughput is better than traditional HPLC or GC-MS, it still falls short of automated immunoassays. Direct sample injection, LC-multiplexing, and sample multiplexing are all evolving methods for increasing LC-MS throughput. Sample cleaning and chromatography optimization are two ways to further improve specificity and sensitivity by avoiding interferences and ion suppression caused by sample matrix components. Additional advantages may be available to the LC-MS platform with next-generation instruments. Among other matters, peptide/protein analysis is the next barrier for clinical LC-MS/MS. The search for multi-biomarker profiles for various diseases has largely failed by LC-MS so far. Still, targeted peptide and protein testing by LC-MS/MS, directed at analytical and clinical questions that need answering, is proving extremely effective. We anticipate that clinical protein/peptide LC-MS/MS will grow at a similar rate to low molecular weight applications.

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