Preparation, characterization of major degradation products of Pralatrexate injection

December 12, 2018

The major degradation products of pralatrexate drug product formed under hydrolytic and light stress conditions were identified, synthesized and characterized using advanced spectroscopic techniques such as NMR, HR-MS and IR. For quantification of related compounds including the degradation products of pralatrexate drug product a stability indicating HPLC method was developed and validated as per ICH guidelines.

Pralatrexate is an antineoplastic folate analog which is chemically named as (2S)-2-[[4-[(1RS)-1-[(2,4-diaminopteridin-6-yl)methyl]but-3-ynyl]benzoyl]amino] pentanedioic acid. Pralatrexate injection is a preservative-free, sterile, isotonic, non-pyrogenic clear yellow aqueous solution for intravenous administration. Chemical stability is an important product quality attribute of the pharmaceutical molecule that affects the safety, quality and efficacy of drug product. The information on the stability of a molecule helps in developing proper formulation, container-closure as well as storage conditions and shelf life. To understand the stability of molecule it is necessary to study degradation profile of a product. The samples generated from forced degradation can help in establishing stability indicating method and also degradation path way of product which helps to predict degradation products arise during accelerated and long term storage conditions. Forced degradation study for drug product is also very important for identifying as well as to know the nature of the degradation products (hydrolytic/oxidation/ heat) and to elucidate the structure of the drug products generated during stress study. To understand the degradation pathway of products an efficient analytical method is required which should be able to detect the impurities generated from stress conditions. High Performance Liquid Chromatography and HR-MS are the best tools to study the impurity profile of degradation products. It is also important to develop a sensitive HPLC method which should be able to detect and quantify the impurities at lower level. To know the detection level of degradation products in a HPLC method, pure forms of impurities are required. Four major degradation products pralatrexate finished product were synthesized and characterized by NMR, FTIR and HR-MS spectroscopic techniques. A sensitive and stability indicating HPLC method was developed and validated for quantification of pralatrexate and degradation products as well related compounds of pralatrexate in pralatrexate liquid formulation.

Bentham Science Publishers

Related Molecule Articles from Brightsurf:

Towards next-generation molecule-based magnets
Magnets are to be found everywhere in our daily lives, whether in satellites, telephones or on fridge doors.

Well-known molecule not found in cancer cells after all
A new research result from Aarhus University shows that a so-called circular RNA molecule, which has been designated as carcinogenic, is actually not found in the cancer cells.

Self-imaging of a molecule by its own electrons
Researchers at the Max Born Institute (MBI) have shown that high-resolution movies of molecular dynamics can be recorded using electrons ejected from the molecule by an intense laser field.

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.

Old molecule, new tricks
Fifty years ago, scientists hit upon what they thought could be the next rocket fuel.

The molecule that can AUTAC bad proteins
Tohoku University researchers have developed a strategy that could help cells get rid of disease-related debris.

Molecule properties change through light
Green light affects this chemical compound in a different way than blue light.

The role of a single molecule in obesity
A single molecule, derived from cholesterol, lurks inside your bloodstream and will increase your body fat, even if you don't eat a diet filled with red meat and fried food.

New molecule maps cerebrovascular system
Peptide developed in Brazil is capable of binding to the blood-brain barrier that protects the central nervous system and could help create novel imaging tests to diagnose Alzheimer's and Parkinson's.

Searching for the surface of water through a single molecule
By observing the spectroscopic behavior of single water molecules embedded in a super-cold, cage-like molecular structure, researchers have revealed key features that underlie the diffuse vibrational spectra of hydrogen-oxygen bonds that make studying the two-dimensional surface structure of water a challenge.

Read More: Molecule News and Molecule Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to