TIDES

Specialist analytical services for therapeutic oligonucleotides and synthetic peptides, the fastest-growing modalities in contemporary pharmaceutical development.

The term TIDES designates two of the most dynamic and rapidly growing therapeutic modalities in the contemporary pharmaceutical industry: therapeutic oligonucleotides and synthetic peptides. Although structurally different, these modalities share a characteristic that distinguishes them from conventional small molecule drugs and large-format biologics: they are molecules of intermediate chemical complexity, synthesised in a controlled manner but with properties that bring them closer to biological modalities in terms of specificity of action, required analytical sensitivity and regulatory stringency.

Therapeutic oligonucleotides — including antisense oligonucleotides (ASOs), small interfering RNA (siRNA), therapeutic mRNA, aptamers and splice-switching oligonucleotides — act by modulating gene expression at the nucleic acid level, offering the possibility of addressing targets previously considered inaccessible to conventional pharmacology. Synthetic peptides, in turn, range from short chemically synthesised peptides to complex designer peptide molecules, with applications spanning oncology, metabolic disease and endocrinology.

The analysis of these modalities requires specialised analytical platforms, dedicated scientific expertise and a thorough understanding of the applicable regulatory frameworks, which combine elements of both small molecule and biologics regulation. AMSbiopharma has developed a specific portfolio of analytical services for TIDES, covering both R&D and bioanalysis needs and those of CMC characterisation and quality control.

The regulatory framework applicable to TIDES services is inherently dual: bioanalysis and PK/PD services fall within the scope of Good Laboratory Practice (GLP) in accordance with OECD guidelines and the bioanalytical guidance of the EMA and FDA, while CMC characterisation and quality control services respond to the principles of Good Manufacturing Practice (GMP). Some advanced characterisation services may also be performed in non-regulated environments for exploratory phases of development. To determine the most appropriate framework for your programme, we invite you to consult our team.

 

Therapeutic oligonucleotides

Therapeutic oligonucleotides are short nucleic acid chains — typically between 15 and 30 nucleotides — designed to bind specifically to target RNA or DNA sequences and modulate their function. The incorporation of chemical modifications into the phosphodiester backbone and sugars — such as phosphorothioate groups, 2’-O-methyl modifications or locked nucleic acids (LNA) — is essential to improve stability against nucleases, optimise pharmacokinetics and reduce immunogenicity.

These modifications, which are precisely what confer therapeutic properties on oligonucleotides, also represent the primary challenge for their analytical characterisation: methods must be capable of precisely confirming the complete sequence of the oligonucleotide, identifying and quantifying impurity species — including truncated sequences, insertions and deletions — and evaluating the stability of the product against its various degradation pathways.

Synthetic peptides

Synthetic therapeutic peptides constitute a therapeutic class of enormous structural and functional diversity, ranging from short linear peptides of a few amino acids to complex cyclic molecules with multiple disulfide bridges or unnatural modifications. Their synthesis by solid-phase peptide chemistry (SPPS) enables the controlled production of highly specific molecules, but also generates a characteristic profile of process-related impurities — truncated peptides, insertion peptides, amino acid deletions — that must be identified, characterised and controlled in accordance with the requirements of ICH Q3A and ICH Q3B.

Therapeutic peptides include both innovative products — such as GLP-1 receptor agonists in diabetes and obesity, antimicrobial peptides or cell-penetrating peptides — and generic versions of established peptide drugs, for which the demonstration of analytical equivalence with the reference medicine is a key regulatory requirement.

Shared analytical challenges

Both subcategories of TIDES share the need for high-resolution analytical platforms — particularly UHPLC with ion-pairing chromatography and high-resolution mass spectrometry (HRMS) — capable of resolving and quantifying molecular species with minimal differences in mass or sequence. Tandem mass spectrometry (MS/MS) is essential for sequence confirmation and structural identification of impurities, while bioanalysis methods in biological matrices demand exceptional sensitivity and specificity given the structural similarity between the drug and endogenous species.

Our catalog of services include

Metabolomics applications

Pharmacokinetic (PK/PD) Analysis / NON GLP

Accurate quantification of drug concentrations in biological matrices is the foundation of every pharmacokinetic programme. Our PK bioanalytical services support pharmacokinetic and preclinical toxicokinetic studies, providing the quantitative data required to characterise drug exposure throughout the development process.

We develop and validate bioanalytical methods for a wide range of biological matrices, including plasma, serum, whole blood, urine, cerebrospinal fluid (CSF), tissue homogenates, and dried blood spots (DBS). Full method development and validation are performed in accordance with ICH M10, covering specificity, selectivity, sensitivity, linearity, accuracy, precision, matrix effects, stability, and dilution integrity.

PK/PD data are delivered in formats compatible with leading pharmacokinetic and pharmacometric modelling software, enabling seamless integration into the sponsor’s development workflows. All studies are conducted under controlled documentation systems aligned with applicable regulatory requirements.

Key analytical capabilities

  • Full ICH M10-compliant bioanalytical method development and validation for regulated studies 
  • Bioanalysis of plasma, serum, urine, CSF, tissue homogenates, and alternative biological matrices 
  • PK/PD data support for dose selection, exposure assessment, and regulatory submissions 
  • Applicable to small molecules, therapeutic peptides, biologics, oligonucleotides, and gene therapy vectors

Drug Metabolism and Pharmacokinetics (DMPK) studies provide a mechanistic understanding of how a compound is absorbed, distributed, metabolised, and excreted (ADME). This information is essential for predicting in vivo behaviour, optimising compound properties, and assessing the potential for drug–drug interactions (DDIs).

AMSbiopharma provides comprehensive DMPK bioanalytical support using both preclinical species and human-derived matrices. Our services include metabolic stability studies in hepatic matrices, metabolite profiling and identification by high-resolution mass spectrometry (HRMS), plasma protein binding, and blood-to-plasma partitioning. Metabolite identification studies are performed to standards suitable for regulatory submissions.

Our team delivers early-stage ADME screening to support lead selection and optimisation, as well as comprehensive, regulatory-grade metabolite profiling studies to support clinical development programmes.

Key analytical capabilities:

  • Metabolic stability screening in liver microsomes, hepatocytes, and S9 fractions

  • Metabolite profiling and structural identification by high-resolution mass spectrometry (HRMS)

  • Plasma protein binding and blood-to-plasma ratio determination

  • Support for reactive metabolite risk assessment and drug–drug interaction (DDI) studies

Stability studies provide the analytical data required to establish shelf life, define storage conditions, and support regulatory submissions. A well-designed stability programme supported by validated stability-indicating analytical methods is a regulatory requirement under ICH Q1 for all drug substances and drug products.

AMSbiopharma supports ICH Q1-compliant stability programmes with validated stability-indicating methods for the determination of assay, degradation products, related substances, and other critical quality attributes. Our team manages sample receipt, analytical testing, and data management throughout the study. Analytical testing is performed using HPLC-UV, HPLC-MS/MS, and GC-MS/MS, as appropriate for the product and analytical requirements.

Key analytical capabilities:

  • Design, execution, and analytical support for ICH Q1-compliant stability studies

  • Validated stability-indicating methods using HPLC-UV, HPLC-MS/MS, and GC-MS/MS

  • Data management compliant with 21 CFR Part 11 and EU GMP Annex 11

Appearance is a fundamental quality attribute of pharmaceutical products and a mandatory release test for all dosage forms. Deviations in colour, clarity, or particulate matter from predefined specifications may indicate product degradation, contamination, or manufacturing process failure.

AMSbiopharma performs validated appearance testing for colour, clarity, and particulate matter using calibrated visual and instrumental methods in accordance with applicable pharmacopoeial specifications and regulatory requirements.

Key analytical capabilities:

  • Visual and instrumental appearance testing in accordance with Ph. Eur. and USP

  • Colour assessment against pharmacopoeial reference standards

  • Clarity testing for solution-based pharmaceutical products

  • Particulate matter testing, including sub-visible particle analysis

  • Applicable to parenteral, oral liquid, and semi-solid dosage forms

  • Supporting documentation for batch release and stability studies

Assay and dosage unit uniformity are fundamental quality control requirements for all pharmaceutical products, providing quantitative evidence that each batch contains the intended amount of drug substance, uniformly distributed throughout the dosage units.

AMSbiopharma employs validated analytical methods across a broad range of analytical platforms, including UV/Vis spectrophotometry, HPLC and UHPLC with multiple detection techniques, GC, GC/MS, and LC/MS, selecting the most appropriate technology for each product. All methods are developed and validated in accordance with the Ph. Eur., USP, and ICH Q2(R2) guidelines.

Key analytical capabilities:

  • Validated assay methods using UV/Vis, HPLC/UHPLC, GC, GC/MS, and LC/MS

  • Content uniformity testing in accordance with Ph. Eur. 2.9.40 and USP <905>

  • Applicable to solid, liquid, semi-solid, and parenteral dosage forms

  • Method development and validation in accordance with Ph. Eur., USP, and ICH Q2(R2)

  • Analytical support for method development, validation, and routine batch release testing

  • Complete documentation to support regulatory submissions

The control of related substances—including process-related impurities, synthetic impurities, and degradation products—is one of the most critical quality control activities in pharmaceutical manufacturing. Regulatory authorities require all drug substances and drug products to be tested down to established reporting thresholds, with any impurity present at or above the applicable identification or qualification thresholds being appropriately identified and qualified.

AMSbiopharma provides validated analytical services for the identification and quantification of related substances using HPLC, GC/MS, and LC/MS, selecting the most appropriate analytical platform based on the physicochemical properties of each compound. Analytical methods are developed and validated in accordance with ICH Q3A(R2), ICH Q3B(R2), and ICH Q2(R2).

Key analytical capabilities:

  • Validated HPLC, GC/MS, and LC/MS methods for the quantification of related substances

  • Detection and quantification at or below the reporting thresholds defined in ICH Q3A(R2) and ICH Q3B(R2)

  • Applicable to drug substances, intermediates, and drug products

  • Impurity profiling in accordance with ICH Q3A(R2) and ICH Q3B(R2)

  • Support for impurity limit justification and toxicological qualification

  • Routine quality control testing with comprehensive supporting documentation

Physical and physicochemical characterization provides critical quality attribute (CQA) data for pharmaceutical products. For liquid and semi-solid dosage forms, parameters such as pH, viscosity, and osmolality are critical determinants of product stability, while for parenteral products, they are essential to ensure physiological compatibility.

AMSbiopharma offers a comprehensive range of validated physicochemical testing services, covering the full spectrum of analytical parameters required for pharmaceutical development and quality control. All analyses are performed using calibrated and qualified instrumentation to ensure reliable, reproducible, and regulatory-compliant results.

Key analytical capabilities:

  • pH measurement across a wide range of pharmaceutical dosage forms

  • Viscosity determination using calibrated instrumentation

  • Density and relative density determination using validated methods

  • Refractive index measurement for identity confirmation and concentration determination

  • Osmolality determination by the freezing-point depression method for parenteral products

Residual solvent testing is a mandatory pharmaceutical quality requirement under ICH Q3C(R9), which classifies solvents according to their toxicological risk and establishes permitted daily exposures (PDEs), reporting thresholds, and acceptance limits. Regulatory authorities require validated analytical methods with sufficient sensitivity to detect and quantify residual solvents below the specified limits.

AMSbiopharma provides validated headspace GC-MS methods for the quantification of ICH Q3C Class 1, Class 2, and Class 3 residual solvents, as well as volatile organic impurities, in drug substances, drug products, and excipients. Headspace gas chromatography coupled with mass spectrometry (HS-GC-MS) delivers the selectivity and sensitivity required for regulatory compliance and routine quality control.

Key analytical capabilities:

  • Validated headspace GC-MS methods for ICH Q3C Class 1, Class 2, and Class 3 residual solvents

  • Detection and quantification at or below the limits specified in ICH Q3C(R9)

  • Applicable to drug substances, drug products, and excipients

  • Method development and validation in accordance with ICH Q3C(R9) and ICH Q2(R2)

  • Analytical support for regulatory submissions and routine quality control testing

  • Profiling of volatile organic impurities beyond those specifically addressed in ICH Q3C(R9)

The bioanalysis of therapeutic oligonucleotides and gene therapy vectors in biological matrices requires analytical approaches with significantly greater complexity and sensitivity than those used for conventional small-molecule drugs. The structural similarity between the active therapeutic and endogenous nucleic acid species places exceptional demands on method sensitivity, specificity, and selectivity.

AMSbiopharma provides validated PK/PD bioanalytical services for oligonucleotide therapeutics, supporting preclinical and translational development programmes with robust quantitative data generated using state-of-the-art bioanalytical methodologies.

Key analytical capabilities:

  • Validated bioanalysis of antisense oligonucleotides (ASOs), RNA interference (RNAi) therapeutics, mRNA therapeutics, and viral DNA/RNA in biological matrices

  • Bioanalytical capabilities for plasma, serum, tissue, and cerebrospinal fluid (CSF)

  • ICH M10-compliant method development and validation

  • Analytical support for tissue distribution and biodistribution studies

Reliable quantification of nucleic acid species and the assessment of gene expression changes in biological matrices are critical analytical requirements for the development of gene therapies and RNA-based therapeutics.

AMSbiopharma provides validated bioanalytical services for the quantification of DNA and RNA targets in biological matrices, including the assessment of gene expression changes relevant to pharmacodynamic monitoring and safety evaluation. Method development and validation are performed in accordance with applicable regulatory guidelines, ensuring robust, reproducible, and regulatory-ready data.

Key analytical capabilities:

  • Quantification of DNA and RNA targets in plasma, tissue, and other biological matrices

  • Gene expression analysis to support pharmacodynamic biomarker programmes

  • Method development and validation in accordance with applicable regulatory guidelines

  • Analytical support for preclinical development programmes

  • Applicable to RNA therapeutics and gene therapy vector programmes

  • Comprehensive documentation to support regulatory submissions

Genetic biomarkers play an increasingly important role in modern drug development, providing mechanistic and predictive insights that support patient stratification, pharmacodynamic monitoring, and precision medicine approaches.

AMSbiopharma provides validated analytical services for the detection and quantification of genetic biomarkers in biological samples. Our methods are developed for regulatory use in both preclinical and clinical studies, with biomarker strategies aligned with current regulatory qualification guidelines.

Key analytical capabilities:

  • Detection and quantification of genetic biomarkers in biological samples

  • Biomarker strategies aligned with regulatory expectations and qualification frameworks

  • Applicable to oncology, rare diseases, and gene therapy programmes

  • Method development for preclinical studies

Extractables and leachables (E&L) represent a critical safety consideration for pharmaceutical products in contact with primary packaging components, container closure systems, drug delivery devices, and manufacturing process contact materials. Leachable compounds migrating from these materials into the drug product may pose potential risks to patient safety and product quality.

AMSbiopharma provides comprehensive Extractables and Leachables (E&L) analytical services aligned with ICH Q3E, including extractables studies to characterise the extractable profile of packaging and process contact materials, leachables studies performed on drug products under appropriate storage conditions, and the preparation of Analytical Evaluation Reports (AERs) to support regulatory submissions.

Analytical studies are performed using HPLC-UV, LC-MS/MS, and GC-MS platforms to ensure broad chemical coverage, applying risk-based approaches that prioritise compounds of greatest toxicological and regulatory relevance.

Key analytical capabilities:

  • Extractables studies for packaging materials, container closure systems, and manufacturing process contact materials

  • Leachables studies in drug products under defined storage conditions

  • HPLC-UV, LC-MS/MS, and GC-MS analytical platforms providing broad chemical coverage

  • Analytical Evaluation Reports (AERs) prepared in accordance with ICH Q3E

Process-related impurities arising from starting materials, reagents, catalysts, solvents, and manufacturing processes must be identified, characterised, and controlled within established limits. In accordance with ICH Q3A(R2) and ICH Q11, manufacturers are required to demonstrate adequate control of these impurities throughout the product lifecycle.

AMSbiopharma provides validated analytical services for the detection, identification, and quantification of process-related impurities in drug substances and drug products, using HPLC, LC-MS, and GC-MS methods selected according to the physicochemical properties of the target impurities.

Key analytical capabilities:

  • Detection and identification of process-related impurities using HPLC, LC-MS, and GC-MS

  • Quantification at or below the reporting thresholds defined in ICH Q3A(R2)

  • Applicable to drug substances, intermediates, and drug products

  • Analytical support for impurity limit justification and regulatory submissions

  • Method development and validation in accordance with ICH Q3A(R2) and ICH Q2(R2)

  • Routine quality control testing with comprehensive documentation and full traceability

The structural identification of unknown drug impurities is a regulatory requirement under ICH Q3A(R2) and ICH Q3B(R2) whenever an impurity is present at or above the applicable identification threshold. Reliable structural elucidation requires the application of multiple orthogonal analytical techniques to achieve a high level of confidence in impurity identification.

AMSbiopharma provides comprehensive unknown impurity identification services using HPLC/UHPLC, high-resolution LC-MS, tandem mass spectrometry (MS/MS), and GC-MS to deliver confident structural elucidation of unknown peaks detected in drug substances and drug products.

Key analytical capabilities:

  • Structural elucidation using HPLC/UHPLC, high-resolution LC-MS, and GC-MS

  • MS/MS fragmentation analysis for confident structural confirmation

  • Applicable to impurities in drug substances and drug products

  • Identification of degradation products, synthetic impurities, and process-related impurities

  • Studies performed in accordance with ICH Q3A(R2) and ICH Q3B(R2), with submission-ready reports

Accurate and reproducible quantification of drug-related impurities—including degradation products, synthetic impurities, and process-related impurities—is a mandatory analytical requirement throughout pharmaceutical development and commercial manufacturing.

AMSbiopharma provides validated analytical services for impurity quantification using HPLC/UHPLC, LC-MS, and GC-MS, with methods developed and validated in accordance with ICH Q3A(R2), ICH Q3B(R2), and ICH Q2(R2). Our methods provide the sensitivity required to detect and quantify impurities at or below the applicable reporting and qualification thresholds.

Key analytical capabilities:

  • Validated HPLC/UHPLC, LC-MS, and GC-MS methods for impurity quantification

  • Detection and quantification at or below the reporting and qualification thresholds defined in ICH Q3A(R2) and ICH Q3B(R2)

  • Applicable to drug substances and drug products throughout all stages of development

  • Method development and validation in accordance with ICH Q3A(R2), ICH Q3B(R2), and ICH Q2(R2)

  • Analytical support for impurity profiling, pharmaceutical development, and regulatory submissions

Comprehensive analytical characterization of therapeutic peptides requires a multi-method approach covering primary structure, sequence integrity, purity, related substances, and physicochemical properties. For generic peptide products, the analytical programme must also address analytical comparability with the reference product.

AMSbiopharma provides characterization services for therapeutic peptides. Primary structure and sequence integrity are confirmed using mass spectrometry, with high-resolution intact mass analysis and peptide mapping providing comprehensive molecular characterization.

Key analytical capabilities:

  • Sequence confirmation and integrity assessment by high-resolution intact mass analysis and peptide mapping

  • Purity and related substances profiling using HPLC methods

  • Structural characterization of cyclic, modified, and conjugated peptides

  • Applicable to linear peptides, cyclic peptides, disulfide-bonded peptides, and backbone-modified peptides

Amino acid analysis provides essential compositional information for the identity confirmation and quality control of proteins, peptides, and amino acid-based pharmaceuticals. Amino acid composition serves as an identity test, a tool for protein content estimation, and a quantitative quality control assay for formulated products.

AMSbiopharma provides validated analytical services for the quantification of amino acids and related compounds in drug substances, drug products, and biological matrices, applying validated hydrolysis and derivatisation protocols followed by chromatographic separation and detection.

Key analytical capabilities:

  • Amino acid composition analysis for protein and peptide identity confirmation

  • Quantification of all proteinogenic amino acids

  • Applicable to drug substance characterization and quality control

  • Support for protein content estimation by amino acid analysis

  • Applicable to drug substances, drug products, and biological matrices

  • Complete validation documentation for regulatory submissions

Peptide mapping is one of the most powerful and informative analytical characterization techniques for protein and peptide therapeutics. By enzymatically digesting the protein into defined peptide fragments and analysing the resulting mixture by LC-MS/MS, peptide mapping provides comprehensive sequence coverage, confirms primary structure integrity, and detects post-translational modifications (PTMs) and chemical degradation at the molecular level.

AMSbiopharma provides validated peptide mapping services using optimised digestion protocols and LC-MS/MS analysis, delivering high sequence coverage together with confident identification and localisation of post-translational modifications, including glycosylation, oxidation, deamidation, phosphorylation, and disulfide bond assignment.

Key analytical capabilities:

  • LC-MS/MS-based peptide mapping with high sequence coverage

  • Identification and localisation of post-translational modifications

  • Glycosylation site mapping and glycopeptide characterization

  • Disulfide bond mapping and free cysteine determination

  • Monitoring of deamidation, oxidation, and other chemical degradation products

Accurate and sensitive quantification of synthetic therapeutic peptides in complex biological matrices is a specialised bioanalytical requirement for PK/PD studies and clinical pharmacology programmes. The structural similarity of peptide therapeutics to endogenous peptides, combined with their susceptibility to enzymatic degradation, requires carefully developed analytical methods to ensure sensitivity, selectivity, and stability.

AMSbiopharma provides LC-MS/MS bioanalytical services for the detection and quantification of synthetic therapeutic peptides in plasma, serum, urine, and other biological matrices, with full method validation in accordance with ICH M10.

Key analytical capabilities:

  • LC-MS/MS methods for the quantification of synthetic peptides in biological matrices

  • Method development addressing peptide stability, sample extraction, and analytical sensitivity

  • Applicable to plasma, serum, urine, and other biological matrices

Toxin-based therapeutics require specialised analytical expertise for the characterization and quality control of highly potent molecules with complex structural attributes.

AMSbiopharma has extensive experience in the analytical characterization of therapeutics derived from natural, recombinant, and novel toxins, applying validated methods for identity confirmation, purity and impurity profiling, potency assessment, and structural integrity evaluation.

Key analytical capabilities:

  • Identity confirmation and structural characterization by mass spectrometry

  • Purity and impurity profiling to support regulatory submissions

  • Applicable to immunotoxins, bacterial toxins, and toxin-derived conjugates

Heparins and glycosaminoglycans (GAGs) are structurally complex, highly sulfated polysaccharide therapeutics that require specialised analytical approaches. The inherent microheterogeneity of these polydisperse molecules, together with their complex charge density, makes their analytical characterization particularly challenging.

AMSbiopharma provides validated analytical services for the characterization and quality control of unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs), covering molecular weight distribution, anticoagulant potency determination, structural characterization, and impurity profiling, including the detection of oversulfated chondroitin sulfate (OSCS).

Key analytical capabilities:

  • Molecular weight distribution analysis by size-exclusion chromatography (SEC) or polyacrylamide gel electrophoresis (PAGE)

  • Anticoagulant potency determination using validated chromogenic assays

  • Structural characterization by disaccharide composition analysis

  • Detection of OSCS and other adulterants for safety assessment

  • Impurity profiling in accordance with Ph. Eur. and USP requirements

  • Applicable to UFH, LMWHs, and novel glycosaminoglycans

Our method development services begin with a comprehensive understanding of the analytical challenge: the physicochemical properties of the analyte, matrix complexity, regulatory context, and performance requirements. Based on this foundation, we design analytical methods optimized for sensitivity, specificity, accuracy, and robustness.

Method validation is performed in accordance with applicable regulatory guidelines — ICH Q2(R2) for quantitative pharmaceutical methods and ICH M10 for regulated bioanalytical methods — covering all required validation parameters: specificity, linearity, range, accuracy, precision, detection and quantification limits, robustness, and stability. Complete validation reports are prepared in a regulatory-ready format.

Method transfer services ensure that validated methods perform consistently in receiving laboratories, through an interlaboratory comparability exercise demonstrating equivalent performance. Transfer documentation complies with applicable regulatory requirements.

Key analytical capabilities:

  • Method development for HPLC, UHPLC, GC, LC-MS/MS, HRMS, and other analytical platforms

  • Full validation in accordance with ICH Q2(R2), ICH M10, and applicable specific guidelines

  • Validation for small molecules, peptides, biologics, and oligonucleotides

  • Method transfer with interlaboratory comparability and regulatory documentation

  • Phase-appropriate validation strategies for early- and late-stage development programs

Accurate molecular weight determination of intact or reduced protein therapeutics by mass spectrometry provides fundamental identity data, confirming primary structure integrity and the presence of any modifications that alter the molecular mass.

AMSbiopharma applies high-resolution mass spectrometry for intact protein and middle-up analysis, with online desalting or deglycosylation performed where appropriate. Charge state deconvolution software generates accurate average and monoisotopic molecular masses for protein species, while isoform distributions are quantified based on relative signal abundance.

Key analytical capabilities:

  • Intact protein molecular weight determination by high-resolution mass spectrometry

  • Middle-up analysis of antibody fragments (Fc, Fab, scFv)

  • Glycoform distribution mapping by intact mass spectrometry

  • Charge state deconvolution for accurate molecular mass determination

  • Applicable to mAbs, Fc fusion proteins, ADCs, bispecific antibodies, and other biologics

Characterization of the interaction between a therapeutic molecule and its protein target provides essential information for pharmacological characterization and mechanism of action studies. Quantitative assessment of target engagement provides mechanistic evidence that the drug reaches and binds to its intended target in vivo.

AMSbiopharma provides analytical services for the evaluation of drug–protein engagement, applying mass spectrometry-based approaches to generate quantitative data on drug–target interactions, supporting mechanism of action characterization and structure–activity relationship studies.

Key analytical capabilities:

  • Mass spectrometry-based approaches for covalent and non-covalent interactions

  • Applicable to diverse therapeutic modalities and target protein classes

  • Support for mechanism of action characterization studies

  • Analytical support for structure–activity relationship data

  • Integration with pharmacodynamic biomarker program design

Exact mass measurement by high-resolution mass spectrometry provides the most definitive identity confirmation available for therapeutic oligonucleotides, delivering a precise molecular formula that confirms the number and identity of constituent nucleotides, backbone modifications, and any other chemical modifications incorporated into the active substance.

AMSbiopharma offers validated exact mass measurement services for therapeutic oligonucleotides using UHPLC coupled to high-resolution mass spectrometry under ion-pair chromatography conditions. Charge-state deconvolution software provides deconvoluted average and monoisotopic masses.

Key analytical capabilities:

  • Exact mass determination with sub-ppm accuracy for therapeutic oligonucleotides

  • Coverage of ASOs, siRNA, aptamers, and highly modified species

  • High-resolution UHPLC-MS with ion-pair chromatography

  • Charge-state deconvolution for intact oligonucleotide mass determination

  • Applicable to phosphorothioate species, 2′ modifications, and other backbone modifications

  • Identity confirmation data for CMC regulatory submissions

Purity assessment is a critical batch release and stability monitoring assay for therapeutic oligonucleotides, ensuring that the active substance meets its purity specification and that process-related impurities — including truncated sequences (n-1, n-2), deletion sequences, extended sequences (n+1), and other synthetic by-products — are within acceptance criteria.

AMSbiopharma provides validated UHPLC-based analytical services for purity determination and impurity identification, applying ion-pair reversed-phase chromatography with UV detection for quantification and mass spectrometry detection for impurity identification.

Key analytical capabilities:

  • Purity determination by validated UHPLC-UV using ion-pair chromatography

  • Chromatographic resolution of n-1, n-2, and n+1 sequence impurities

  • Impurity identification by LC-MS for structural characterization

  • Applicable to ASOs, siRNA, aptamers, and modified oligonucleotides

  • Support for CMC development.

Sequence confirmation provides definitive identity verification for therapeutic oligonucleotides, ensuring that the active substance contains the intended nucleotide sequence and that all chemical modifications are present at the correct positions. It is a mandatory component of the identity characterization package for regulatory submissions.

AMSbiopharma provides validated sequence confirmation services using tandem mass spectrometry (MS/MS)-based approaches, generating fragment ion series that confirm the nucleotide sequence and localize chemical modifications throughout the entire length of the oligonucleotide.

Key analytical capabilities:

  • MS/MS-based sequence confirmation with comprehensive sequence ion coverage

  • Identification and localization of backbone and base modifications

  • Confirmation of phosphorothioate linkages, 2′ modifications, and other backbone features

  • Regulatory-grade sequence identity data for CMC submissions

  • Support for short and long oligonucleotides

Stability and degradation analysis for therapeutic oligonucleotides provides essential information for shelf-life determination, storage condition specification, and understanding of degradation pathways. ICH Q1-compliant stability programs require validated stability-indicating analytical methods capable of detecting the full range of degradation products.

AMSbiopharma provides validated analytical services for stability and degradation assessment, applying UHPLC and LC-MS/MS platforms to detect, quantify, and identify degradation products.

Key analytical capabilities:

  • Validated stability-indicating UHPLC methods for formal ICH Q1-compliant stability studies

  • Detection and quantification of degradation products

  • Identification of degradation products and pathway elucidation by LC-MS/MS

  • Applicable to active substance and drug product stability programs

  • Coverage of hydrolytic, oxidative, and depurination degradation pathways

Microbial enumeration testing of non-sterile pharmaceutical products is a fundamental requirement for ensuring product quality and patient safety. Determination of the Total Aerobic Microbial Count (TAMC) and the Total Yeast and Mould Count (TYMC) provides the quantitative evidence required to demonstrate compliance with the microbiological acceptance criteria established in the applicable pharmacopoeial specifications, confirming that the microbial bioburden remains within acceptable limits throughout the product’s shelf life.

AMSbiopharma performs validated TAMC and TYMC testing in accordance with Ph. Eur. 2.6.12/2.6.13 and USP <61>/<62>, including the method suitability studies required for each product type and matrix. All testing is carried out under controlled laboratory conditions by qualified personnel following documented procedures aligned with Good Manufacturing Practice (GMP) principles.

Method validation includes assessment of method suitability for each product type, incorporating the recovery studies required by Ph. Eur. 2.6.12/2.6.13 and USP <61>/<62>. Test results are provided with comprehensive supporting documentation suitable for batch release and stability programmes.

Key analytical capabilities:

  • Total Aerobic Microbial Count (TAMC) in accordance with Ph. Eur. 2.6.12 and USP <61>

  • Total Yeast and Mould Count (TYMC) in accordance with Ph. Eur. 2.6.13 and USP <62>

  • Testing of active pharmaceutical ingredients (APIs), drug products, excipients, and raw materials

Microbiological testing of water is a critical component of the quality assurance system in pharmaceutical manufacturing facilities. The microbiological quality of water used during manufacturing—including Purified Water (PW), Water for Injection (WFI), and Highly Purified Water (HPW)—is a critical quality attribute that must be routinely monitored in accordance with the requirements of the Ph. Eur., the USP, and applicable GMP guidelines.

AMSbiopharma provides microbiological testing services for pharmaceutical water using methods compliant with applicable pharmacopoeial and regulatory requirements. Our services include microbial enumeration testing (TAMC/TYMC) and the detection of specified microorganisms, in accordance with the water quality specifications established by the Ph. Eur. and the USP for each pharmaceutical water grade.

Key analytical capabilities:

  • Microbiological testing of Purified Water (PW), Water for Injection (WFI), and Highly Purified Water (HPW)

  • TAMC/TYMC determination and detection of specified microorganisms in pharmaceutical water in accordance with Ph. Eur. and USP requirements

Antimicrobial preservatives are critical formulation components in many multidose pharmaceutical products, including ophthalmic, parenteral, oral, and topical preparations. Demonstrating preservative efficacy—its ability to prevent microbial proliferation and maintain the microbiological integrity of the product throughout its intended storage and in-use period—is a mandatory regulatory requirement that must be assessed using Antimicrobial Preservative Effectiveness Testing (AET) in accordance with applicable pharmacopoeial methods.

AMSbiopharma performs Antimicrobial Preservative Effectiveness Testing (AET) in compliance with Ph. Eur. 5.1.3 and USP <51>, using the pharmacopoeia-required challenge panel of bacteria, yeasts, and moulds, and applying the acceptance criteria established for each product category. All studies are conducted using certified reference strains under controlled laboratory conditions, with comprehensive documentation suitable for inclusion in regulatory submissions.

Key analytical capabilities:

  • Antimicrobial Preservative Effectiveness Testing (AET) in accordance with Ph. Eur. 5.1.3 and USP <51>

The quantification of biological indicators and specific microorganisms is an essential component of a wide range of pharmaceutical microbiology applications, including sterilisation process qualification and validation, pre-sterilisation bioburden determination, and the monitoring of manufacturing processes where control of specific microorganisms is critical to product quality and patient safety.

AMSbiopharma provides biological indicator quantification and microorganism enumeration services using validated methods tailored to each specific application. Biological indicators are microorganisms with a defined and characterised resistance to the sterilisation process under evaluation—typically Geobacillus stearothermophilus spores for steam sterilisation and Bacillus atrophaeus spores for ethylene oxide sterilisation. Their quantification before and after the sterilisation process provides documented evidence of sterilisation process effectiveness.

Key analytical capabilities:

  • Pre-sterilisation bioburden determination in accordance with Ph. Eur. 2.6.12 and ISO 11737-1

  • Enumeration of specific microorganisms in product and process samples

Bacterial endotoxins are lipopolysaccharides (LPS) found in the outer membrane of Gram-negative bacteria. When introduced into the body through parenteral products, they can trigger severe pyrogenic reactions and, in extreme cases, septic shock. Consequently, bacterial endotoxin testing is a critical quality attribute for all parenteral pharmaceutical products and a mandatory requirement for batch release.

Key analytical capabilities:

  • Bacterial Endotoxins Testing (BET) using the Limulus Amebocyte Lysate (LAL) method in accordance with Ph. Eur. 2.6.14 and USP <85>