Drug release testing service

According to ICH regulatory requirements, any one of the analytical method needs to be validated and confirmed before it can be used to release and test,

Testing scope

API, intermediates, starting materials, chemical products, etc

Guiding principles

Chinese Pharmacopoeia -- CHP 2015 Edition, 2020 Edition

United States Pharmacopoeia - the latest edition of the USP

European Pharmacopoeia - the latest edition of EP

Japanese Drugstores - the latest edition of JP

ICH guidelines -Q series, M series

Quality system

Strictly follow the requirements of ISO17025, and refer to the relevant provisions of cGMP


Properties: appearance, physical constant test(melting point, optical rotation)

Identification: general identification, infrared, ultraviolet, X-ray powder diffraction, NMR, mass spectrometry.

Inspection: related substances, residual solvent, water contents, ash, pH value, drying weight loss, incandescent burning residue, chloride, heavy metal, particle size, etc.

Assay: high performance liquid chromatography, gas chromatography, ultraviolet spectrophotometry, potentiometric titration, mass spectrometry, ion chromatography


Chromatography: high performance liquid chromatograph (VWD, DAD, CAD), gas chromatograph (FID)

Molecular spectrum: ultraviolet - visible spectrophotometer, infrared spectrophotometer

Mass spectrometry: high performance liquid chromatography-mass spectrometry (HPLC-MS/MS), gas chromatography-mass spectrometry (GC-MS/MS), inductively coupled plasma mass spectrometry (ICP-MS)

Titration: potential titrator, Karl Fischer moisture analyzer, Coulomb Karl Fischer moisture analyzer

Physical and chemical categories: melting point instrument, high precision digital polarimeter, differential scanning calorimeter, thermogravimetric analyzer, laser particle size analyzer

Business Development

PQP, DHA releasing and testing


Genotoxic Impurities Research Services

Genotoxic impurities are impurities that are found to be potentially damaging to DNA in in vitro/in vivo experiments with DNA reactive substances as the main research objects

Risk of genotoxic impurities

Under current regulations, genotoxic substances have the potential to damage DNA at any level of intake, and this damage could lead to the development of tumors. Therefore, for genotoxic carcinogens, it cannot be said that "there is no clear threshold or that any level of ingestion is associated with a risk of carcinogenesis".

Acceptable Risk Intake

A TTC value of "1.5ug/day", equivalent to 1.5ug of genotoxic impurities daily, is considered an acceptable risk for most drugs (lifetime cancer risk is less than 100,000/1). Based on this threshold, an acceptable level of impurity in the active drug can be calculated based on the expected daily intake.

Guiding principles

ICH Q3A Impurities in New API

ICH Q3B Impurities in New Pharmaceutical Preparation

ICH M7 "Evaluation and control of DNA reactivity (mutagenic) impurities in drugs to limit potential carcinogenic risk"

China CDE: Technical Guiding Principles for the Standardization Process of the Establishment of Chemical Drug Quality Standards

Technical Guiding Principles for Validation of Analytical Methods for Chemical Drug Quality Control

Technical Guiding Principles for the Study of Chemical Drug Impurities,

"Chinese Pharmacopoeia" four general rules 0431, 0513

Impurity classification

ClassificationDefinitionControl strategy
Mutagenicity and carcinogenicity are knownControl within acceptable limits of the compound
Mutagenicity known, carcinogenicity unknown (bacterial mutation test positive, but no rodent carcinogenicity data)Control within acceptable limits (appropriate TTC)
It has warning structure, has no relation to API structure, and has no mutagenicity data

Control to acceptable limits (suitable TTC) or detect bacterial mutations if not mutagenic, control as class 5 if mutagenic, control as class 2

It has the same warning structure as the drug itself and no mutagenicity dataControlled by non-genotoxic impurities
There is a warning structure or sufficient data to indicate that the warning structure is not mutagenic or carcinogenicControlled by non-genotoxic impurities

Research strategy

According to the physical properties of genotoxic impurities, such as volatilization, molecular weight, ultraviolet absorption, boiling point, etc., different methods were used to quantify the impurities.

Business Development

Determination of NDMA in Metformin (LC-MS/MS, GC-MS/MS), N-nitroso amine in Sartans (LC-MS/MS, GC-MS/MS), Hydroxylamine in Sartans (Ion Chromatography-Electrochemical Method)

The warning structures of genotoxic impurity


Elemental Impurity Research Services

source of elemental impurities: elemental impurities include those that may be present in raw materials, excipients or preparations, from catalyst residues in synthesis,

Elemental impurity classification


Elemental impurities

Whether to conduct a risk assessment


Class 1



The elements arsenic (As), cadmium (Cd), mercury (Hg) and lead (Pb) are toxic substances to humans and should not be used or restricted in pharmaceutical production, usually from mineral excipients. Therefore, these four elements must be evaluated in risk assessments for all routes of administration.

Class 2A



Cobalt (Co), nickel (Ni), vanadium (V). The presence of elements with a relatively high probability in medicinal products requires a risk assessment of all potential sources of elemental impurities and all routes of ingestion.

Class 2B


Only when added deliberately

Silver (Ag), gold (Au), iridium (Ir), osmium (Os), palladium (Pd), platinum (Pt), rhodium (Rh), ruthenium (Ru), selenium (Se), thallium (Tl), these elements are rare in nature and are less likely to appear in drugs. May be excluded from the risk assessment unless it is intentionally added to the manufacture of an active drug substance, excipient or other component of the drug product.

Class 3



It depends on the route of administration

These elements include barium (Ba), chromium (Cr), copper (Cu), lithium (Li), molybdenum (Mo), antimony (Sb), and tin (Sn). These elements have relatively low toxicity when ingested orally but need to be considered in risk assessment for inhalation and injection administration. Oral administration, unless intentionally added to the manufacture of an active drug substance, excipient, or other component of the drug product, does not need to be considered in the risk assessment. For injection and inhalation, the likelihood of the presence of these elements should be evaluated in the risk assessment unless the route of administration is PDE in excess of 500ug/day.

Class 4

B、Fe、Zn、K、Ca、Na、 Mn、Mg、W、Al


These elemental impurities are less toxic and/or have different requirements in local regulations that do not specify PDE and are not stated in this guide. If these elements are present or included in medicinal products, they are dealt with in accordance with other guidelines or regional regulations. Such elements include aluminum (AL) and boron (B), calcium (Ca), iron (Fe), potassium (K), magnesium (Mg), manganese (Mn), sodium (Na), tungsten (W), zinc (zinc). Aluminium, for example, impairs kidney function, and manganese and zinc are harmful to patients with liver dysfunction.

Guiding principles

Formulate assessment and control strategies for elemental impurities, assess the elemental impurities in APIs and preparations based on ICH guidelines and relevant requirements of national pharmacopoeias, and provide scientific control strategies

Relevant guidelines and pharmacopoeia:ICH Q3D "Guidelines for Elemental Impurities", USP<232>"Guidelines for Elemental Impurities", USP<233 bbb="">Determination and Method Verification of Elemental Impurities ", "Chinese Pharmacopoeia" four general rules 0412

Research strategies

Based on the concept of QBD, relevant control thresholds were established according to dosage forms.Detection Method: Inductively Coupled Plasma Mass Spectrometry (ICP-MS)

Business Development

Determination and methodological verification of Pb, Cd, Hg, As, Co, V, Ni in raw materials and oral preparations

Development and validation of elemental impurity analysis methods, development of more than a dozen elemental impurity analysis methods.

Impurity identification research services

Significance of impurity identification:the safety and effectiveness of drugs is an important basis to evaluate the quality of drugs.

Guiding principles

ICH Q3D Guidelines for Elemental Impurities

USP<232>Guidelines for Elemental Impurities

USP<233>"Determination and verification of elemental impurities"

Chinese Pharmacopoeia four general rules 0412

Business Development

Testing and Certification Center Structure Verification team is dedicated to the identification and evaluation of relevant substances in the process of drug research. Under the guidance of cGMP system, the research team provides research services such as attribution analysis, structure verification (identification), quantitative nuclear magnetic evaluation (impurity COA) of relevant substances. Qualitative and quantitative analysis of starting materials, intermediates and API were carried out by using NMR, chromatography and mass spectrometry.

Main instrument testing items

Structure verification: IR, UV, NMR, XRD, MS, DSC and TGA, OR(elemental analysis) and structure analysis


instrument and equipment

research contents

infrared spectroscopy

ThermoFisher Summit

Functional group matching, crystal shape

ultraviolet spectroscopy

Mettler TOLEDO UV7

Ultraviolet absorption spectra

400M、600MNMR spectrometer

Zhongke NIUJIN NMR spectrometer

1D 1H, 13C, 15N, 31P, 19F experiment; 2D 1H-1H COSY, 1H-19F COSY, HMCC, HSQC, HMBC, NOESY, TOCSY, ROESY experiment

XRD poweder diffraction

Marvin Panaco Empyrean XRD Powder Diffractometer

Drug crystal analysis

mass spectrum

(1) Gas chromatography-triple quadrupole mass spectrometer (Agilent 8890-7000D)

(2) Gas chromatography-quadrupole mass spectrometer

(Agilent 8890-5977B)

(3) Four-stage Rod Electrostatic Field Orbitwell High Resolution Mass Spectrometer (High Resolution)

(Semofey QE Focus)

(4) Three-in-One Ultra-High Resolution Mass Spectrometer (High Resolution) (Semofei QE Fusion)

(5) Liquid chromatography-time-of-flight mass spectrometer (Agilent 1260II-6230B)

(6) liquid chromatography-triple quadrupole mass spectrometer

(7) liquid chromatography-quadrupole mass spectrometer

(1) Qualitative and quantitative analysis of volatile and semi-volatile organic compounds

(2) Unknown compound structure analysis, unknown impurity structure analysis, proteomics analysis

(3) Identification and characterization of small and macromolecular compounds, drug development, toxicological studies, and recombinant protein analysis 

Differential scanning calorimetry (DSC)


Qualitative and quantitative analysis of materials; Melting point, glass transition temperature, crystallinity, heat of melting and crystallization, purity of drugs, polycrystalline analysis of drugs


Measure the dry weightlessness and crystal water of the sample

Elemental analysis

Aglient 1260II-7800 ICP-MS

Most metallic elements and some non-metallic elements can be analyzed. Multi-element simultaneous determination, high accuracy, detection limit up to PPB or even PPT level

Drug quality research services

Purpose of quality research: quality research is an important part of quality control, and it is a comprehensive, systematic and in-depth quality research on the products developed.

Assay of drug quality research

5.Analyze the physicochemical and biological properties of the drug itself, investigate the factors of impurities and purity of various drugs, so as to  establish the characteristics of the drug, identification, inspection, assay and other inspection or determination items, storage conditions, etc.

API: focus on the physicochemical and biological properties, stability, impurity and purity control of the drug itself

Preparation: Based on API, it focuses on safety, availability, uniformity and stability

Drug stability study: Drug stability is the ability to keep physicochemical properties and biological properties unchanged. Investigate the change rule of drugs with time under the influence of temperature, humidity, light and other factors, which includes influence factor experiment, accelerated test, long-term test.

Quality control research includes

6.preparation technology research, structure confirmation research, formulation technology research, product quality research and quality standard formulation, and stability research, etc.

Guiding principles

ICH Q6A Quality Standards: Methods and Acceptable Standards for the Detection of New API and New Pharmaceutical Products

ICH Q6B Quality Standards: Methods and Acceptable Standards for the Detection of Biotechnology Products and Biological Products

ICH Q2(R1) Validation of Analytical Methods

CDE in China:

Technical Guiding Principles for the Standardization Process of the Establishment of Chemical Drug Quality Standards;

Technical Guiding Principles for Validation of Analytical Methods for Chemical Drug Quality Control

Technical Guiding Principles for the Study of Chemical Drug Impurities

"Chinese Pharmacopoeia" four general rules 9101

Business Development

7.Quality control of API;

Development and verification of analytical methods;

Establishment of quality standards for starting materials, intermediates and APIs, including development and verification of methods for studying and determining particle size of related substances, optical isomers, assay, residual solvents, genotoxic impurities, elemental impurities, and structural verification, physical and chemical testing;

Acquisition of central control data in synthesis process research.

Process safety assessment service

7.Quality control of API; Development and verification of analytical methods;Establishment of quality standards for starting materials, intermediates and APIs

Guiding principles

Guidelines for Safety Assessment of Fine Chemical Reactions (Trial)

Guiding Opinions of the State Administration of Work Safety on Strengthening Risk Assessment of Fine Chemical Reaction (Safety Supervisor No.3 [2017] No. 1)

Safety analysis of hazardous chemicals/reaction heat

Including: melting point of material, initial decomposition temperature, partial release heat;

Real-time temperature, pressure, stirring torque, volume and other changes of the reaction;

Heat accumulation and kinetic data of the reaction.

Optimization of chemical processes in pharmaceutical and fine chemical industries

Monitor the changes of parameters such as temperature, heat and pressure in the process of chemical reaction, physical mixing, distillation and crystallization, optimize the process conditions and improve the essential safety of production.

Instruments and equipment

Mettler Toledo DSC3 differential scanning calorimeter:

As a result of the modular design, from production, quality assurance to technical development and other processes are applicable. The instrument uses a robust and versatile DSC sensor with 56 pairs of thermocouples to ensure both excellent resolution and sensitivity. Equipped with automatic sampler,  all-weather efficient and reliable operation conditions can be provided.

The instrument is mainly used to measure the thermal stability of fine chemicals, the glass transition temperature Tg, melting temperature Tm, crystallization temperature Tc of polymer materials, and the energy absorbed or released. It is used to understand the crystallinity and purity of the substance, study the crystallization kinetics of the substance, and explore the substance.

Mettler Toledo RC1 automatic reaction calorimeter:

Mentler Toledo's fully automated reaction calorimeter, RC1MX, can be used to intuitively simulate and evaluate pilot-scale or larger reactions. The Icontrol software matching the first phase has the function of modular design, which can realize the full automation of most test reactions through simple modular design and programming with UCB comprehensive control box. The supporting ICSAFETY software can process and display the real-time signal data acquired by the sensor, and calculate the experimental parameters used for evaluation on this basis. In addition, the instrument is also equipped with safety brake facilities and voltage regulator power supply, which can maximize the safety of the instrument and the surrounding environment in the event of equipment failure or reaction out of control. The instrument has the characteristics of high accuracy, safe and reliable, accurate results, intuitive and simple operation, and powerful data processing function, which is an important hardware support for safety risk assessment.

- Main technical applications 

The instrument is mainly used to measure the heat release rate of the reaction process, the specific heat capacity of the reaction system (CP), the highest possible temperature of the uncontrolled system (MTSR), the total heat release of the reaction (Q) and the adiabatic temperature rise (△Tad).

-Services available 

① Chemical reaction safety risk assessment

In accordance with the national safety supervision bureau on strengthening fine chemical reaction risk assessment work guidance of "three (2017) no. 1 】 【 safety manager's requirements, to the catalogue of key regulatory dangerous chemical process full version (2013) contains 18 classes focus on regulation of dangerous chemical process and metal organic synthesis reaction for safety risk assessment.

② Safety analysis of hazardous chemicals/reaction heat Include: Measurement of various thermal data (e.g., heat of reaction), monitoring of reaction progress (reaction starting point, end point and kinetics), process safety assessment and amplification (△Tad, MTSR, Cp, U)

③ Optimization of chemical processes in pharmaceutical and fine chemical industries

Monitor the changes of parameters such as temperature, heat and pressure in the process of chemical reaction, physical mixing, distillation and crystallization, optimize the process conditions and improve the essential safety of production.

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