Reference Standards are highly characterized substances used as a benchmark in analytical testing. In the pharmaceutical industry, they are essential for ensuring the identity, purity, strength, and quality of medicines — whether you're working with active pharmaceutical ingredients (APIs), impurities, or excipients.
Here’s how Reference Standards are commonly used:
Method validation: Establish that your analytical methods are capable of accurately detecting and quantifying APIs, impurities (even at trace levels), or excipients.
Routine quality control: Ensure ongoing accuracy and consistency in batch release testing, including assay, content uniformity, and impurity profiling.
Procedure verification: Confirm that your testing methods perform reliably under your laboratory’s specific conditions.
Calibration of instruments: Generate precise calibration curves, especially critical when quantifying impurities or performing potency assays.
Impurity identification and quantification: Use impurity standards for peak identification, limit testing, and to support stability and degradation studies.
Method development and optimization: Support the creation of robust analytical procedures throughout R&D and manufacturing.
Estimation of measurement uncertainty: Reference Standards help quantify variability in your results, reinforcing data integrity and regulatory compliance.
By using qualified reference standards, you strengthen the reliability of your results — supporting regulatory submissions, product development, and routine quality assurance across all stages of a pharmaceutical product`s lifecycle.
Klivon Scientific provides three distinct tiers of Reference Standards—Elemental, Dynamic, and Beyond—each designed to meet different stages of pharmaceutical R&D and quality control needs. Below is a quick guide to help you understand the strengths of each category and decide which fits your application best:
Best for: Early-stage development, academic research, or qualitative screening
Confirm identity and structure using primary techniques: ¹HNMR (400 MHz), ¹³CNMR, FTIR, MS and purity by HPLC with guaranteed purity > 90%
Ideal for R&D or impurity identification when cost-efficiency is key and full assay data may not be critical yet
Best for: Routine non-compendial testing or initial QC method validation
Upgraded identity confirmation (¹H/¹³CNMR at 500 MHz), FTIR, MS
Purity ≥ 95% by HPLC, assay ≥ 90% by the 100% formula
Water content determination by KF or TGA
Comes with tailored remarks for each technique with final conclusions from our experts
Offers excellent cost-efectiveness for many ICH/FDA/WHO compliant applications
Best for: High-impact or regulated environments requiring maximum standard characterization
Full identity confirmation: ¹H/¹³CNMR (500 MHz), HRMS, FTIR
HPLC purity ≥ 97%, assay ≥ 95% using the 100% formula
Detailed structural elucidation reports and comprehensive spectrum interpretation
Recommended for regulatory filings, stability studies, impurity profiling, forced-degradation, and critical QA/QC
We guarantee a minimum HPLC Purity for each of the following categories:
• Elemental – HPLC Purity Range >95%
• Dynamic – HPLC Purity Range >95%
• Beyond – HPLC Purity Range >97%
In very general terms, we can divide the product categories into those intended for qualitative and quantitative analyses. Please see the diagram below for a more illustrative explanation. In any case, do not hesitate to contact our team, and we will be happy to help you find the best option for your needs. Please remember that at Klivon, we tailor our products to the specific requirements of each client.
1. Klivon Elemental (qualitative use) – Analyses included in the CoA: 1H-NMR and C13-NMR, MS, IR, HPLC
2. Klivon Dynamic (quantitative use) – Analyses included in the CoA: 1H-NMR and C13-NMR, MS, IR, HPLC, CHN, TGA or KF, Assay value (100% formula)
3. Klivon Beyond (quantitative use) – Fully characterized high-purity reference standard; in addition to the analyses already included in the Dynamic category, the CoA incorporates further complementary analytical techniques for assay determination, such as residual solvents by NMR and the orthogonal method for purity determination. A more detailed report including spectral interpretation is also provided.
After reviewing the most appropriate analytical techniques for your product and confirming our capacity to carry out its characterization, you may send us a sample of the batch you wish to use as a reference standard. We will then perform the characterization, which includes the issuance of a Certificate of Analysis (CoA). Please note that this CoA applies exclusively to the submitted batch and not to any other batches.
Depending on the type of characterization requested, different quantities are required. On average, the approximate minimum amounts are as follows:
• 200 mg for Elemental characterization,
• 300 mg for Dynamic characterization,
• 500 mg for Beyond characterization.
These values represent the estimated minimum quantities. If possible, we recommend providing slightly larger amounts – for instance, around 600 mg for Dynamic characterization. Nevertheless, please note that depending on the molecule, specific analytical requirements may differ, and the quantities required may vary accordingly.
Klivon does not work with expiry dates but rather with retest dates. This means that we assign a retest date based on the molecular characteristics that ensure stability over time. Accordingly, the CoA will include a retest date, after which a new analysis must be performed to confirm that purity is maintained. If purity is confirmed, the retest date is extended, and the standard may continue to be used.
We establish the retest periods for our products on the basis of scientific and technical criteria, in accordance with the applicable international guidelines, such as ICH Q1A(R2), ICH Q7, ICH Q3A/B, and ISO 17034 recommendations.
Our stability assessment practices and the determination of retest periods are fully aligned with these principles, aiming to ensure maximum reliability and traceability of your products.
We believe it is relevant to highlight the possible origins of primary reference standards, according to the ICH (International Conference on Harmonization) guidelines:
1. Obtained from an officially recognized source,
2. Prepared by independent synthesis,
3. Obtained from existing high-purity production material,
4. Prepared by further purification of existing production material.
Based on this, a primary reference standard is a substance obtained from any of these sources, proven to be authentic and of high purity through an extensive set of analytical tests. These standards are supplied by Klivon and can be used for any analytical method (whether pharmacopoeial monograph methods or not).
Pharmacopoeial standards, on the other hand, are commonly referred to as compendial standards and hold a special status for use in monograph methods. These standards must be used for pharmacopoeial methods and may not be suitable for other purposes.
Klivon offers customized packaging options. You may select from a range of different pack sizes or specify the exact quantity you require, and we will adjust both the packaging and the price accordingly.
Klivon establishes the re-test periods for its products based on scientific and technical criteria, in accordance with applicable international guidelines such as ICH Q1A(R2), ICH Q7, ICH Q3A/B, and ISO 17034 recommendations.
The process for defining re-test periods takes the following parameters into account:
1. Nature and physicochemical characteristics of the molecule
- Molecular structure and presence of sensitive functional groups.
- Potential for chemical or physical degradation.
2. Stability data
- Results from accelerated and long-term stability studies, conducted in accordance with ICH Q1A(R2) guidelines.
- Data from reliable scientific literature or from reference raw material suppliers.
3. Hygroscopicity
- Water uptake capacity assessed through gravimetric analysis or equivalent techniques.
- Risk of changes in mass, purity, or physical appearance as a function of relative humidity.
4. Packaging and storage conditions
- Type of primary packaging and protective barrier.
- Specified temperature and humidity ranges for preservation.
5. Historical experience and performance records
- Batch history of materials with similar characteristics and synthesis processes.
Based on these parameters, the re-test period is determined individually for each batch to ensure that the material remains compliant with the specifications stated in the respective Certificate of Analysis (CoA) until the established date.
In accordance with ISO 17034 guidelines, the assigned re-test periods are valid only if the product is stored under the specified conditions. Klivon conducts periodic reassessments and may revise or update re-test periods in light of new technical data, historical evidence, or regulatory requirements.
Klivon defines minimum Purity and Assay specifications for each product category (Elemental, Dynamic and Beyond) based on a robust analytical framework and typical physicochemical behavior of pharmaceutical reference standards.
However, there are two specific cases where these values may not be strictly applicable:
1. Highly hygroscopic compounds
For hygroscopic materials, moisture uptake is an intrinsic and reversible physicochemical property governed by equilibrium with ambient humidity. As a result, measured assay and purity values are influenced by water content rather than chemical degradation. In such cases, results are determined and interpreted based on controlled water quantification (e.g., Karl Fischer or TGA) and may be reported on different analytical bases (as-is, dried, or mass balance).
2.. Custom synthesis products
For tailor-made compounds, particularly early-stage or structurally complex molecules, the achievable purity and assay are inherently dependent on synthetic feasibility, compound stability, and intended use. As such, purity levels are not predefined but are established following comprehensive analytical characterization of the final material and in many cases aligned with the project requirements. The suitability of the product for its intended application, including use as an analytical standard, is assessed based on the full set of analytical data generated.
In all cases, Klivon ensures:
Full transparency in the Certificate of Analysis (CoA)
Clear indication of analytical methods and reporting basis
Scientifically justified specifications consistent with the material characteristics
This approach ensures both analytical reliability and practical applicability for research and quality control purposes.
Rather than applying generic specifications, Klivon prioritizes scientifically justified values tailored to each molecule.
Minimum specifications are defined based on typical physicochemical behavior; however, certain compounds require a more scientifically tailored approach.
For highly hygroscopic materials, moisture uptake is an intrinsic and reversible phenomenon governed by environmental equilibrium, directly impacting mass balance and assay results without indicating any loss of chemical integrity. In such cases, values depend on the analytical basis (as-is, dried or anhydrous) and controlled water determination.
For custom synthesis products, achievable purity and assay are influenced by synthetic feasibility, molecular stability, and equilibrium phenomena (e.g., isomerism or degradation pathways). Specifications are therefore established case-by-case, aligned with the intended analytical application.
Additionally, factors such as stability over time, solid-state properties, and residual volatiles may influence reported values, reinforcing the importance of scientifically justified specifications rather than fixed generic thresholds.
