Laboratory Testing Case Studies

Challenge: The prostacyclin derivative is a starting material in the manufacturing of a tricyclic benzidene prostacyclin analog with pharmacologic actions similar to those of Epoprostenol.  Epoprostenol improves exercise capacity and survival in patients with pulmonary arterial hypertension.  The prostacyclin analog is also efficacious by subcutaneous infusion, it is easier to administer and has a longer half-life.  Determination of this prostacyclin derivative and its impurities is central to developing a deep understanding of a commercial manufacturing process.

Challenge: The objective of this project at Diteba was to develop methods for complete compositional analysis of Krill Oil. Such characterization included total lipid / fat content, phospholipids, free fatty acids, triglycerides, cholesterol esters, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, lysophosphatidylcholine, sterols, cholesterol, sigmasterol, sigmastanol, sitosterol, vitamin D-3, vitamin E, and carotenoids: canthaxanthin, astaxanthin.

Challenge: Diteba's main objective of this study was to develop a simple, reliable and reproducible in vitro quality control method that could be used to discriminate variation in release characteristics of NNRTI solid dose formulations to assure batch-to-batch uniformity.  Diteba's scientists attempted to develop a methodology that could be used to discriminate formulation changes, and evaluate the precision, reproducibility and sensitivity for in vitro release rate study (IVRT) experiments.

Challenge: Diteba undertook research with the technological objective to develop a suitable procedure that was capable of detecting and quantifying all nine main components in an energy soft drink: caffeine, niacin, vitamin B₆, pantothenic acid, riboflavin, vitamin B₁₂, taurine, glucuronolactone and inositol. The procedure was intended for use in quality control testing and long-term stability testing of energy drinks.

Challenge: To develop and validate a chiral HPLC method capable of monitoring the purity of a Triazole analogue in a novel production process and two other methods: LC/MS/MS for identification of process impurities; and a head space GC method capable of qualitatively and quantitatively monitoring residual organic volatile impurities (OVI) during the manufacturing process.

Challenge: The goal of this work was to investigate the improvement of resolution between all multimer, dimer and monomers in a monoclonal antibody (mAb).  The method was initially developed by the sponsor but failed to demonstrate adequate level of sensitivity and selectivity when used during stability studies.  In addition the resolution between the analytes (monomer, dimer and multimer) was very poor.

Challenge: Typical oligonucleotides used as therapeutics or potential therapeutic compounds are 15 to 30 nucleotides (nt) long. Oligonucleotides <15 nt can be readily resolved by HPLC technology, however the separation of longer sequences are more challenging. Ion-pair reversed-phase (IP-RP) HPLC has been traditionally used for oligonucleotides analysis.  The traditional IP-RPLC eluent system typically uses TEA or TEAA or HFIP and the ion-pairing agent triethylammonium ion and a C18, column at 60^oC. Under such conditions, the column's hydrolytic stability becomes crucial and is important to prevent the potential contribution of the oligonucleotide secondary structure from impacting retention.

Challenge: The objective of this project was to develop simple, precise, rapid and reproducible analytical methods for the quantification of: a) major Ginsenosides in Panax quinquefolius extract; and b) Flavonols in Ginkgo Biloba extract and use these methods as quality control tools for commercial energy drink products.

Non-nucleoside reverse transcriptase inhibitors (NNRTI's) are antiretroviral drugs used in the treatment of human immunodeficiency virus (HIV).  NNRTI's inhibit reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of HIV.  RT is one of the most popular targets in the field of antiretroviral drug development.  However, separation of all 7 peaks achieved by gradient elution in 45 minutes total run time was unacceptable due to a high sample throughput during stability and quality control programs.  The development of a new rapid and more efficient UPLC^TM analytical method was necessary to overcome the shortcomings of the existing HPLC method.

Challenge: Diteba was commissioned by a sponsor to conduct research for the development of an analytical method for in vitro determination of the release rate of sulfanilamide in topical vaginal cream. The method was developed and based on a modified Franz Diffusion Cells fitted with synthetic membranes.