BOC Sciences, as a global leading ADC comprehensive service platform, has long been focused on the design, synthesis, process development, and quality control of ADCs, with services covering the entire spectrum from early research to GMP-level large-scale production. In ADC development, the drug-to-antibody ratio (DAR) is a critical quality attribute that directly affects the efficacy, safety, pharmacokinetics, and clinical performance of ADCs. BOC Sciences possesses a complete set of mature and precise DAR analysis platforms, integrating advanced techniques such as LC-MS, UV-Vis, CE-SDS, and ESI-MS, to provide global clients with high-resolution, high-sensitivity, and quantitatively accurate DAR analysis services.
DAR directly determines the amount of drug delivered by each ADC molecule. Through high-precision DAR analysis, developers can identify the optimal DAR range during the candidate molecule screening phase, thus finding the best balance between efficacy and safety.
The DAR of traditional nonspecific ADC preparations ranges from 0 to 8. DAR data can be used to optimize key parameters such as conjugation conditions, reaction time, and drug loading ratio, ensure the consistency and controllability of different production batches, and reduce the risk of quality deviation.
DAR analysis can dynamically track the changes in drug-to-antibody ratio, reveal the stability of the conjugation bond, and provide data support for ADC formulation development, cold-chain transportation management, and shelf-life setting, ensuring the stability of the final product's quality.
BOC Sciences offers end-to-end DAR analysis services covering the entire lifecycle, from ADC molecule design verification, process optimization to clinical filing, ensuring clients have solid data support for quality control and regulatory compliance. Additionally, for different ADC conjugation methods adopted by clients, such as non-specific chemical conjugation (lysine conjugation/cysteine conjugation), enzyme-catalyzed conjugation, site-specific modifications, or click chemistry conjugation, BOC Sciences provides the most suitable analysis method development, optimization, and validation services. We build DAR analysis strategies based on pharmacopoeia requirements and the QbD concept, ensuring data accuracy, repeatability, compliance, and traceability, fully supporting clients in preparing technical documentation and regulatory communication during the IND, NDA, and BLA stages.
DAR value measurement of the initial conjugation product to quickly assess drug loading efficiency as a basis for process development and optimization.
High-resolution DAR analysis of purified ADC samples, combined with mass spectrometry, to verify their structure and conjugation site integrity.
Using techniques such as HIC or LC-MS to accurately analyze the proportion of different DAR subpopulations, revealing ADC distribution uniformity and process stability.
DAR comparison across multiple production batches to assess process reproducibility and product consistency, meeting cGMP quality requirements.
Regularly monitoring DAR changes during long-term or accelerated stability tests to evaluate the chemical stability of the conjugation structure.
Using techniques like SEC-HPLC and mass spectrometry to analyze the relationship between different DAR levels and aggregate formation or ADC purity changes.
Providing standardized DAR analysis reports and data packages for GLP or GMP stage samples, in compliance with ICH and FDA filing regulations.
BOC Sciences' advanced analytical platform is equipped with a wide range of high-end instruments, including high-resolution mass spectrometry (HR-MS), liquid chromatography (HPLC/UPLC), and capillary electrophoresis (CE), enabling precise evaluation of critical attributes such as DAR, purity, aggregates, and stability. Combined with automated sample handling and high-throughput data acquisition capabilities, BOC Sciences not only enhances analytical efficiency but also ensures data reproducibility and traceability.
LC-MS combines the separation ability of liquid chromatography with the high-resolution detection advantage of mass spectrometry, enabling accurate quantification and structural analysis of different DAR subtypes. It is widely used for overall DAR distribution analysis under both reducing and non-reducing conditions and is one of the most commonly used methods for DAR determination.
By measuring the characteristic absorption wavelengths of antibodies and small molecule drugs (such as 280 nm and 250 nm), the average DAR value can be quickly calculated. It is suitable for early screening and batch-to-batch consistency evaluation, easy to operate, and ideal for high-throughput analysis.
CE-SDS separates ADC subunits under reducing or non-reducing conditions, revealing drug modifications on the light or heavy chains. With high resolution and strong sensitivity, it is an important complementary method for indirect characterization of DAR distribution and structural integrity analysis.
HIC utilizes the enhanced hydrophobicity of ADCs with increasing DAR values to separate and quantify different DAR subtypes. It is widely used in heterogeneity studies and conjugation process development and is one of the classic methods for evaluating DAR distribution.
SEC-HPLC separates ADC samples based on molecular size to analyze aggregates, monomers, and degradation products. While it cannot directly measure DAR, it reveals the aggregation trends associated with high DAR and is an important complementary tool in ADC stability analysis.
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry is suitable for quickly screening the molecular weight distribution of small molecule-antibody conjugates. It can assist in confirming ADC configuration and some DAR characteristics, demonstrating high efficiency, especially in the initial assessment following conjugation reactions.
We design and validate custom solutions based on client needs, ensuring accurate reflection of conjugation extent, distribution, and its relation to other characteristics (e.g., purity, aggregates).
We utilize advanced instruments, including UPLC, Q-TOF, Orbitrap mass spectrometers, and laser particle size analyzers. Our equipment is continually updated to handle complex ADC samples, enabling precise DAR measurement and drug loading analysis.
BOC Sciences offers efficient data processing software with visualization tools and automated analysis. Our reports meet international standards and can be customized for FDA, EMA, and other regulatory compliance.
We provide high-throughput ADC screening and quantitative analysis, enhancing efficiency in early R&D, scale-up, and quality control stages. Automated systems allow us to process multiple samples simultaneously, improving speed and accuracy.
Using MS, BOC Sciences accurately analyzes ADC structure, conjugation sites, drug-antibody linkages, and drug loading levels. Our high-resolution Q-TOF and Orbitrap platforms provide detailed molecular insights for ADC optimization and quality control.
All platforms comply with cGMP standards, ensuring data compliance, reliability, and traceability. We adhere to international pharmaceutical regulations, ensuring global regulatory compliance for product registration and clinical trials.
The Drug-to-Antibody Ratio (DAR) refers to the number of drug molecules attached to a single antibody molecule in an Antibody-Drug Conjugate (ADC). It is a critical parameter that impacts the therapeutic efficacy, pharmacokinetics, and safety of ADCs. A higher DAR typically indicates a higher drug loading per antibody, which may enhance the cytotoxicity of the ADC, but excessive drug loading can lead to reduced stability or increased off-target toxicity.
The optimal DAR for an Antibody-Drug Conjugate (ADC) depends on the specific ADC's design, drug payload, and therapeutic goal. Typically, an optimal DAR balances efficacy with safety, often ranging between 2-8 drug molecules per antibody. Lower DARs may improve stability and reduce off-target effects, while higher DARs may enhance the cytotoxic effect but may also increase the risk of toxicity. Finding the optimal DAR requires extensive optimization and in vivo testing for each ADC formulation.
The Drug-to-Antibody Ratio (DAR) is the number of drug molecules attached to each antibody molecule. The method for calculating DAR typically relies on techniques like mass spectrometry (MS) or liquid chromatography (HPLC). By separating different subtypes of the ADC (with varying drug loading levels) and combining quantitative analysis, the number of drug molecules attached to each antibody can be determined. Common calculation methods include determining the mass of the drug and antibody and calculating the average DAR value to provide accurate loading data.
