Liquid Chromatography Coupled Mass Spectrometry

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Liquid Chromatography Coupled Mass Spectrometry

Method Introduction

Mass spectrometry separates ionized molecules according to their mass-to-charge ratio. In combination with prior knowledge of the sample, LC-MS analysis allows for comprehensive insight into the sample on a molecular level.

Our high-resolution quadrupole time-of-light (TOF) mass analyzers can target various analytical questions, coupled with Ultra-High-Performance Liquid Chromatography (UPLC). Most important for pharmaceutical developers are the characterization and quantification of active pharmaceutical ingredients (API) (on a small and large molecule scale) as well as formulation excipients such as surfactants (polysorbates (PS)), saccharides, and amino acids. Each of our systems is dedicated to a particular analytical target.

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Applications

  • Antibodies or proteins, in general, can be analyzed on an intact level (intact mass analysis, also known as top-down approach) or after proteolytic digest on a sub-unit level (middle-up approach) as well as on a peptide level (bottom-up approach). Typically, reversed-phase (RP) chromatography is used to desalt the sample (e.g., in case of intact mass analysis) or to separate protein fragments based on hydrophobicity from each other. Applying volatile buffer systems also allows size exclusion chromatography for aggregation analysis and ion exchange chromatography to analyze protein charge variants.

    Altogether, the method portfolio at Coriolis can be used for biosimilar characterization (e.g., head-to-head comparison of biosimilar and innovator), analysis of post-translational modifications (e.g., C-terminal lysine clipping), and degradation monitoring during stability studies (e.g., deamidation, oxidation).

    Often, several critical quality attributes (CQA) like oxidation, deamidation, and glycation can be accessed via one single method, also called multi-attribute monitoring (MAM).

  • Surfactants are, in many cases, an integral part of biopharmaceutical formulations and crucial for API (e.g., protein) stability during pharmaceutical product shelf life. One of the most common surfactants used in biologics is polysorbate 20 (PS20) or polysorbate 80 (PS80); both are typically used to prevent protein absorption on surfaces and protein aggregation induced by interfacial stresses. Yet, PS degradation can also lead to the formation of particles. Major root causes for PS degradation are i) the inherent tendency for auto-oxidation and ii) residual host cell membrane proteins with enzymatic activity that hydrolyze the PS ester bonds.

    Therefore, close monitoring of PS throughout the shelf life of the pharmaceutical product is essential. Coriolis has profound experience in PS quantification, characterization, and monitoring. At Coriolis, PS analysis is conducted with the help of LC-MS (for in-depth characterization) and LC-charged aerosol detection (CAD) (for high throughput screening). Also, other buffer excipients, such as amino acids or saccharides, can be quantified with the help of reversed-phase (RP) or hydrophilic interaction liquid chromatography (HILIC) coupled to MS or CAD. LC-MS can also be applied to monitor small molecule APIs and to characterize degradation products “popping up” during stability studies with the help of tandem MS.

Quality and Biosafety Level

We provide all our analytical services with the highest quality standards. Experienced scientists carry out each project, and a scientific reviewer comprehensively checks every report or data presentation.

We offer this technology with the following quality and biosafety levels:

R&D level

We offer this method under R&D. Our GRP system assures the highest-quality research standards.

Up to biosafety level 1

This method can be applied to proteins, nucleic acids, and most viral vectors, including AAVs and more.

Analytical Method Development, Qualification and Validation

For common sample types, we can often apply standardized methods with little setup effort. However, when needed, our experienced analytical experts create or optimize custom methods tailored to your active pharmaceutical ingredient, product type and development phase.

Method Development

Our method development approach tailors sample preparation, method settings and data analysis to the needs of your project and sample.

We include representative samples and, where available, suitable reference standards and stressed/degraded materials, allowing our analytical scientists to design a highly suitable, stability-indicating, robust and repeatable method. Upon request, we will compile a detailed description of the method for your records.

Method Qualification

Method qualification is the initial assessment of an analytical procedure’s performance to show its suitability for its intended purpose.

During method qualification, our analytical scientists perform documented testing demonstrating that the analytical procedure meets criteria in several categories. Criteria may include factors such as repeatability, specificity and robustness. We compile a qualification plan and report, including all relevant data.

Method Validation

Under GMP conditions, method validation confirms that an analytical procedure’s performance suits its intended purpose. Depending on the method’s scope, a broad range of method characteristics, such as specificity, accuracy, precision, limit of detection/limit of quantification (LOD/LOQ), linearity and range, is considered.

During method validation, our analytical scientists perform documented testing demonstrating that the analytical procedure consistently produces a result that meets the predetermined acceptance criteria. We compile a validation plan and report that includes all relevant data.

Depending on the development phase, a fit-for-purpose validation approach can be offered, adjusting the validation required efforts in a phase-appropriate way to meet the method’s needs.

Method Verification

Compendial method verification confirms that a compendial method (e.g., from Ph. Eur. or USP) is suitable and reliable for its intended purpose under the specific conditions of the laboratory.

Unlike full method validation, compendial method verification is often considered a partial validation since the method has already undergone extensive testing and validation during its inclusion in the compendium. The extent of method verification depends on the type of method.

During method verification, our analytical scientists perform documented testing demonstrating that the developed analytical method performs adequately for the specific product or matrix being tested and within the specific laboratory where the method will be employed.

Talk to Our Experts or Request a Quote

Our expert team is ready to answer your questions and guide you to the services best suited to your program’s modality, stage and challenge. If your needs are well-defined, we’ll begin the quotation process.

Description

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