PepGenex Science glossary

Short definitions of terms used across PepGenex Science, each with a reference where one exists. Terms with a longer explanation link to their concept page.

Accelerated testing

Stability studies designed to increase the rate of chemical degradation or physical change of a drug substance or product by using exaggerated storage conditions, as defined in ICH Q1A(R2).^[1] Storage conditions in stability guidance

Acceptance criteria

Numerical limits, ranges or other suitable measures for accepting the results of analytical procedures, as defined in ICH Q6B.^[2] Certificate of analysis (COA)

Accuracy

The closeness of agreement between an accepted reference value and the value or values measured by an analytical procedure, as defined in ICH Q2(R2).^[3] Analytical method limitations

Aggregation

A form of physical instability in which protein or peptide molecules associate with one another; Manning and colleagues list it with precipitation, denaturation and surface adsorption.^[4] Lyophilized vs solution stability

Agonist

A ligand that binds a receptor and activates it, so that binding is linked to a response.^[5] Receptor agonist

Amino acid analysis

Quantification of a peptide by hydrolysing it completely and measuring selected chemically stable amino acids released, described by Stoppacher and colleagues as common practice.^[6] Net peptide content

Amino acid residue

What remains of each amino acid after two or more amino acids combine to form a peptide and the elements of water are removed.^[7] Peptide

Antagonist

A ligand that binds a receptor without activating it. Kenakin describes competitive antagonists with negative efficacy as showing inverse agonism where a receptor is constitutively active.^[8] Receptor agonist

Batch (lot)

A specific quantity of material produced in a process or series of processes so that it is expected to be homogeneous within specified limits, as defined in ICH Q7.^[9] Lot traceability

C-terminal

The residue of a peptide that has a free carboxyl group, or at least does not acylate another amino acid residue.^[7] Peptide

Certificate of analysis (COA)

A document for one batch that lists each test performed, the acceptance limits and the numerical results. ICH Q7 section 11.4 describes its contents.^[9] Certificate of analysis (COA)

Collapse temperature

A temperature discussed in freeze-drying process design; Tang and Pikal describe how it and the transition Tg′ inform the target product temperature for primary drying.^[10] Lyophilization (freeze-drying)

Contaminant

Any adventitiously introduced material, such as a chemical, biochemical or microbial species, not intended to be part of the manufacturing process, as defined in ICH Q6B.^[2] Endotoxin vs microbial testing

Counterion

An oppositely charged ion, such as trifluoroacetate, acetate or chloride, that accompanies a charged peptide in its solid salt form.^[11] Counterion content (acetate, TFA, chloride)

Deamidation

A chemical change at asparagine or glutamine residues; Manning and colleagues list it among the chemical instability pathways of proteins, with proteolysis, oxidation and racemization.^[4] Lyophilized vs solution stability

Degradation product

A molecular variant resulting from changes in the desired product over time or by the action of, for example, light, temperature, pH or water, as defined in ICH Q6B.^[2] Lyophilized vs solution stability

Detection limit (DL)

The lowest amount of an analyte in a sample that can be detected but not necessarily quantitated as an exact value, as defined in ICH Q2(R2).^[3] Analytical method limitations

Diastereomer

A stereoisomer that is not a mirror image. D'Hondt and colleagues describe diastereomeric impurities in synthetic peptides arising from racemization of amino acid residues.^[12] Counterion content (acetate, TFA, chloride)

DOI

Digital Object Identifier. PepGenex Science cites journal articles by DOI where one exists and links it through doi.org.

Elemental impurity

A metal or metalloid present in a material, either added intentionally, for example as a catalyst, or arising from equipment, container closure systems or components, as described in ICH Q3D(R2).^[13] Heavy metals and elemental impurities testing

Endotoxin

The lipid A domain of bacterial lipopolysaccharide.^[14] Endotoxin testing

Endotoxin unit (EU)

The unit in which endotoxin limits are expressed, for example EU/mL, in FDA's endotoxin guidance and USP chapter <161>.^[15] Endotoxin testing

Epimer

A stereoisomer differing at one stereocenter. Lian and colleagues discuss LC-MS characterization of peptide epimers as impurities of synthetic peptides.^[16] Purity vs identity

Expiry date

The date designating the time during which a material is expected to remain within established shelf life specifications if stored under defined conditions, as defined in ICH Q7.^[9] Storage conditions in stability guidance

G protein-coupled receptor (GPCR)

A receptor with seven membrane-spanning domains that signals through G proteins; Mayo describes the seven domains as a hallmark of the family.^[17],[18] Receptor agonist

Gram-negative bacteria

Bacteria whose outer membrane contains lipopolysaccharide, the source of endotoxin.^[14] Endotoxin testing

HPLC

High-performance liquid chromatography, a separation technique used for the isolation, purification and analysis of peptides in size-exclusion, ion-exchange and reversed-phase modes.^[19] HPLC purity

ICH

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, which develops quality guidelines such as Q2(R2), Q6B and Q7; the U.S. FDA publishes them as guidance.^[3]

ICP-MS

Inductively coupled plasma mass spectrometry, which Lewen and colleagues present as an alternative to the older wet-chemical heavy metals test, with specific detection and quantitation for each element.^[20] Heavy metals and elemental impurities testing

Identity test

A test that confirms a material is the substance it is labeled as. ICH Q6B states that identity tests should be highly specific and may need more than one method.^[2] Identity testing

Impurity

Any component that is not the desired product, a product-related substance or an excipient; it may be process-related or product-related, as defined in ICH Q6B.^[2] HPLC purity

In vitro

Evidence type used on PepGenex Science for studies in cells, tissues or purified molecules outside a living organism. In vitro vs in vivo

Intended use

Under 21 CFR 201.128, the objective intent of the persons legally responsible for a product's labeling, shown by their expressions, the article's design or the circumstances of its distribution.^[21] Research use only (RUO)

Inverse agonist

A ligand with negative efficacy that reduces constitutive receptor activity. In Kenakin's survey, 322 of 380 antagonists studied were inverse agonists.^[8] Receptor agonist

Ion chromatography

A separation technique that Sikora and colleagues describe as the first-choice method for determining counter-ions in peptides.^[11] Counterion content (acetate, TFA, chloride)

LAL

Limulus amebocyte lysate, a reagent from horseshoe crab blood cells that is gelled by endotoxin and is used in bacterial endotoxins tests.^[22],[15] Endotoxin testing

Ligand

A molecule that binds a receptor. Signal transduction links ligand binding to a response.^[5] Receptor agonist

Lipopolysaccharide (LPS)

A molecule of Gram-negative bacteria consisting of lipid A, a core oligosaccharide and an O-antigen polysaccharide.^[14] Endotoxin testing

Long-term testing

Stability studies under the recommended storage condition for the retest period or shelf life proposed for labeling, as defined in ICH Q1A(R2).^[1] Storage conditions in stability guidance

Lyophilization

Freeze-drying: freezing, primary drying by sublimation and secondary drying by desorption.^[23] Lyophilization (freeze-drying)

Mass balance

An approach in which the mass fraction of every impurity is estimated by a range of techniques and the main peptide is assigned the difference from the theoretical limit, as Stoppacher and colleagues describe.^[6] Net peptide content

Mass spectrometry

An analytical technique that measures the mass-to-charge ratio of ions; combined with liquid chromatography (LC-MS) it is used to characterize synthetic peptides and their impurities.^[16],[2] Mass spectrometry (MS)

Membrane filtration

A compendial sterility test format in which the sample is filtered and the membrane is cultured; Parveen and colleagues found it more sensitive than two automated culture systems they evaluated.^[24] Sterility testing

N-terminal

The residue of a peptide that has a free amino group, or at least one not acylated by another amino acid residue.^[7] Peptide

Net peptide content

The proportion of the mass of a solid peptide material that is the peptide itself, rather than counterions, water, residual solvents or inorganic residue.^[11],[25] Net peptide content

Oligopeptide

A peptide with fewer than about 10-20 residues.^[7] Peptide

Peptide

Any compound produced by amide formation between a carboxyl group of one amino acid and an amino group of another.^[7] Peptide

Peptide bond

An amide bond in a peptide.^[7] Peptide

Peptide map

The pattern obtained by fragmenting a product into discrete peptides with enzymes or chemicals and analyzing the fragments, for example by HPLC.^[2] Peptide mapping

PMID

PubMed identifier. PepGenex Science cites journal articles by PMID where one exists and links it to the PubMed record.

Polypeptide

A peptide with more than about 10-20 residues.^[7] Peptide

Precision

The closeness of agreement between a series of measurements from multiple samplings of the same homogeneous sample, as defined in ICH Q2(R2).^[3] Analytical method limitations

Primary drying

The freeze-drying stage in which ice is removed by sublimation.^[23] Lyophilization (freeze-drying)

Protein

A polypeptide of specific sequence of more than about 50 residues, although authors differ on where the term starts.^[7] Peptide

Pyrogen test

The rabbit test described in USP chapter <151>; FDA has accepted an LAL test for endotoxins in lieu of it for more than 30 years.^[26],[15] Endotoxin testing

Quantitation limit (QL)

The lowest amount of analyte in a sample that can be quantitatively determined with suitable precision and accuracy, as defined in ICH Q2(R2).^[3] Analytical method limitations

Quantitative NMR (qNMR)

Quantitative nuclear magnetic resonance, which Melanson and colleagues describe as a way to quantify an intact peptide without the potential bias of a hydrolysis step.^[27] Net peptide content

Range

The interval between the lowest and highest results in which an analytical procedure has a suitable level of response, accuracy and precision, as defined in ICH Q2(R2).^[3] Analytical method limitations

Receptor

A molecule whose function is chemical recognition of signals such as endogenous ligands.^[5] Receptor agonist

Research use only (RUO)

A labeling category. 21 CFR 809.10(c)(2)(i) sets out the statement for in vitro diagnostic products in the research phase; the label alone does not determine regulatory status.^[28],[21] Research use only (RUO)

Retatrutide

A synthetic peptide recorded as an agonist at the glucagon, GIP and GLP-1 receptors, also identified as LY3437943. The abbreviation "RETA" is used for it in the published literature.^[29],[30] Retatrutide on PepGenex Science

Retest date

The date when a material should be re-examined to ensure that it is still suitable for use, as defined in ICH Q7.^[9] Storage conditions in stability guidance

Reversed-phase chromatography

A mode of liquid chromatography used for peptide separation and analysis.^[19],[2] HPLC purity

Secondary drying

The freeze-drying stage in which remaining water is removed by desorption.^[23] Lyophilization (freeze-drying)

Shelf life

The period during which a drug product is expected to remain within its approved specification when stored under the conditions on its label, as defined in ICH Q1A(R2).^[1] Storage conditions in stability guidance

Solid-phase peptide synthesis (SPPS)

Peptide synthesis on a solid support, described by Merrifield in 1963; a 2014 review states that most peptides today are made this way.^[31],[12] Peptide

Specification

A list of tests, references to analytical procedures and acceptance criteria for the tests described, as defined in ICH Q6B.^[2] Certificate of analysis (COA)

Specificity

The ability of an analytical procedure to identify or quantify an analyte without interference from other substances present, as described in ICH Q2(R2).^[3] Analytical method limitations

Sterility test

A microbiological test that examines samples of a material for viable contaminating microorganisms; ICH Q4B Annex 8(R1) considers USP <71> and two other pharmacopoeial texts interchangeable.^[32],[33] Sterility testing

Storage condition

The defined temperature, humidity and, where relevant, light exposure under which a material is held in a stability study and to which its retest period or shelf life is tied.^[1] Storage conditions in stability guidance

Stress testing

Testing that ICH Q1A(R2) asks for to show a drug substance's susceptibility to degradation, including hydrolysis across a wide range of pH values in solution or suspension.^[1] Lyophilized vs solution stability

Trifluoroacetate

A counter ion that can remain in a synthetic peptide from solid-phase synthesis or purification.^[12] HPLC purity

USP

United States Pharmacopeia. Its general chapters are cited by number, for example <85> Bacterial Endotoxins Test.^[34] Endotoxin testing

Validation

Work that demonstrates an analytical procedure is fit for the intended purpose, as described in ICH Q2(R2).^[3] Analytical method limitations