Steven W. Baertschi

article

Artifactual degradation of secondary amine-containing drugs during accelerated stability testing when saturated sodium nitrite solutions are used for humidity control

Gregory W. Sluggett, Todd Zelesky, Evan M. Hetrick, Yelizaveta Babayan, more

Journal of Pharmaceutical and Biomedical Analysis > 2018 > 149 > C > 206-213

Accelerated stability studies of pharmaceutical products are commonly conducted at various combinations of temperature and relative humidity (RH). The RH of the sample environment can be controlled to set points using humidity-controlled stability chambers or via storage of the sample in a closed container in the presence of a saturated aqueous salt solution. Herein we report an unexpected N-nitrosation...

article

Formation of copper(I) from trace levels of copper(II) as an artifactual impurity in the HPLC analysis of olanzapine

Steven W. Baertschi, Bernard A. Olsen, Timothy J. Wozniak, Nick Toltl, more

Journal of Pharmaceutical and Biomedical Analysis > 2016 > 125 > C > 186-193

An analytical artifact peak appearing to be an impurity was observed intermittently among several laboratories performing HPLC analyses of olanzapine drug substance and formulation samples. The artifact peak was identified as Cu(I) that was formed from the reaction of trace amounts of Cu(II) with olanzapine in the sample solution. Unlike Cu(II), Cu(I) was retained under the ion-pairing HPLC conditions...

chapter

Forced Degradation and Its Relation to Real Time Drug Product Stability

Steven W. Baertschi

Biotechnology: Pharmaceutical Aspects > Pharmaceutical Stability Testing to Support Global Markets > Technical Concepts for Stability Program > 107-116

Forced degradation (stress testing) studies are fundamental to the developing stability-indicating analytical methods as part of the overall analytical control strategy. Stress testing studies conducted on both the drug substance and product are useful for gaining an understanding of the degradation chemistry of a drug. The degradation products observed in such studies are “potential” degradation...

article

Artifacts Generated During Azoalkane Peroxy Radical Oxidative Stress Testing of Pharmaceuticals Containing Primary and Secondary Amines

Marcela Nefliu, Todd Zelesky, Patrick Jansen, Gregory W. Sluggett, more

Journal of Pharmaceutical Sciences > 104 > 12 > 4287 - 4298

We report artifactual degradation of pharmaceutical compounds containing primary and secondary amines during peroxy radical‐mediated oxidative stress carried out using azoalkane initiators. Two degradation products were detected when model drug compounds dissolved in methanol/water were heated to 40°C with radical initiators such as 2,2′‐azobis(2‐methylpropionitrile) (AIBN). The primary artifact was...

article

Implications of In‐Use Photostability: Proposed Guidance for Photostability Testing and Labeling to Support the Administration of Photosensitive Pharmaceutical Products, Part 2: Topical Drug Product

Steven W. Baertschi, David Clapham, Chris Foti, Mark H. Kleinman, more

Journal of Pharmaceutical Sciences > 104 > 9 > 2688 - 2701

Although essential guidance to cover the photostability testing of pharmaceuticals for manufacturing and storage is well‐established, there continues to be a significant gap in guidance regarding testing to support the effective administration of photosensitive drug products. Continuing from Part 1, (Baertschi SW, Clapham D, Foti C, Jansen PJ, Kristensen S, Reed RA, Templeton AC, Tønnesen HH. 2013...

article

Investigation of the Mechanism of Racemization of Litronesib in Aqueous Solution: Unexpected Base‐Catalyzed Inversion of a Fully Substituted Carbon Chiral Center

Steven W. Baertschi, Patrick J. Jansen, Robert M. Montgomery, William K. Smith, more

Journal of Pharmaceutical Sciences > 103 > 9 > 2797 - 2808

Mitosis inhibitor (R)‐litronesib (LY2523355) is a 1,3,4‐thiadiazoline‐bearing phenyl and N‐(2‐ethylamino)ethanesulfonamido‐methyl substituents on tetrahedral C5. Chiral instability has been observed at pH 6 and above with the rate of racemization increasing with pH. A positively charged trigonal intermediate is inferred from the fact that p‐methoxy substituent on the phenyl accelerated racemization,...

article

Recent Trends in Product Development and Regulatory Issues on Impurities in Active Pharmaceutical Ingredient (API) and Drug Products. Part 2: Safety Considerations of Impurities in Pharmaceutical Products and Surveying the Impurity Landscape

Karen M. Alsante, Kim C. Huynh-Ba, Steven W. Baertschi, Robert A. Reed, more

AAPS PharmSciTech > 2014 > 15 > 1 > 237-251

Dedication: This manuscript is dedicated to the memory of the late Karen Russo, Ph.D. (United States Pharmacopeial Convention)

article

Recent Trends in Product Development and Regulatory Issues on Impurities in Active Pharmaceutical Ingredient (API) and Drug Products. Part 1: Predicting Degradation Related Impurities and Impurity Considerations for Pharmaceutical Dosage Forms

Karen M. Alsante, Kim Huynh-Ba, Steven W. Baertschi, Robert A. Reed, more

AAPS PharmSciTech > 2014 > 15 > 1 > 198-212

Dedication This manuscript is dedicated to the memory of the late Karen Russo, Ph.D. (United States Pharmacopeial Convention)

article

On-column nitrosation of amines observed in liquid chromatography impurity separations employing ammonium hydroxide and acetonitrile as mobile phase

David P. Myers, Evan M. Hetrick, Zhongming Liang, Chad E. Hadden, more

Journal of Chromatography A > 2013 > 1319 > Complete > 57-64

The availability of high performance liquid chromatography (HPLC) columns capable of operation at pH values up to 12 has allowed a greater selectivity space to be explored for method development in pharmaceutical analysis. Ammonium hydroxide is of particular value in the mobile phase because it is compatible with direct interfacing to electrospray mass spectrometers. This paper reports an unexpected...

article

Implications of In‐Use Photostability: Proposed Guidance for Photostability Testing and Labeling to Support the Administration of Photosensitive Pharmaceutical Products, Part 1: Drug Products Administered by Injection

Steven W. Baertschi, David Clapham, Chris Foti, Patrick J. Jansen, more

Journal of Pharmaceutical Sciences > 102 > 11 > 3888 - 3899

Basic guidance on the photostability testing of pharmaceuticals, designed to cover manufacturing and storage over shelf life, has long been established within ICH Q1(ICH,B¹⁰, but the guideline does not cover the photostability of drugs during or after administration (i.e., under conditions of use). To date, there has been a paucity of guidance covering the additional testing that would be of value...

article

Assessing mass balance in pharmaceutical drug products: New insights into an old topic

Steven W. Baertschi, Brian W. Pack, Cherokee S. Hoaglund Hyzer, Mark A. Nussbaum

Trends in Analytical Chemistry > 2013 > 49 > Complete > 126-136

Mass balance is an important concept in pharmaceutical development, but it often proves challenging to assess accurately. This article explores the various methods by which mass balance can and should be measured, expressed, and evaluated in conjunction with degradation chemistry. Causes of mass-balance issues and potential solutions are summarized, as are the advantages and the disadvantages of various...

article

The role of analytical chemistry in drug-stability studies

Sándor Görög, Steven W. Baertschi

Trends in Analytical Chemistry > 2013 > 49 > Complete > 55-56

article

The assessment of impurities for genotoxic potential and subsequent control in drug substance and drug product

Linda K. Dow, Marvin M. Hansen, Brian W. Pack, Todd J. Page, more

Journal of Pharmaceutical Sciences > 102 > 5 > 1404 - 1418

The strategies implemented at Eli Lilly and Company to address European Medicines Agency and US Food and Drug Administration requirements governing the control of genotoxic impurities (GTIs) are presented. These strategies were developed to provide understanding with regard to the risk and potential liabilities that could be associated with developmental and marketed compounds. The strategies systematize...

article

Prediction of Drug Degradation Pathways leading to Structural Alerts for Potential Genotoxic Impurities

Stephen P. Raillard, Joel Bercu, Steven W. Baertschi, Christopher M. Riley

Organic Process Research & Development > 2010 > 14 > 4 > 1015 - 1020

article

A critical assessment of the ICH guideline on photostability testing of new drug substances and products (Q1B): Recommendation for revision

Steven W. Baertschi, Karen M. Alsante, Hanne H. Tønnesen

Journal of Pharmaceutical Sciences > 99 > 7 > 2934 - 2940

The ICH guideline on photostability (ICH Topic Q1B) was published in November 1996 and has been implemented in all three regions (US, EU, and Japan). The guideline describes a useful basic protocol for testing of new drug substances and associated drug products for manufacturing, storage, and distribution, but it does not cover the photostability of drugs under conditions of patient use. The pharmaceutical...

article

Analytical methodologies for discovering and profiling degradation-related impurities

Steven W. Baertschi

Trends in Analytical Chemistry > 2006 > 25 > 8 > 758-767

The analytical technologies currently in use for profiling degradation-related impurities (DRI’s) are powerful, but not without their limitations. This article critically assesses the technologies, their strengths and limitations, and recommends strategies for successful DRI profiling. Improvements in analytical separations and detection technologies are leading to strategies involving multiple orthogonal...

article

2-Nitrobenzaldehyde: a convenient UV-A and UV-B chemical actinometer for drug photostability testing

John M. Allen, Sandra K. Allen, Steven W. Baertschi

Journal of Pharmaceutical and Biomedical Analysis > 2000 > 24 > 2 > 167 - 178

We report the development of a new 'photochemical titration' actinometric method for measurement of UV-B (290-320 nm) and UV-A (320-400 nm) light dose during drug photostability testing. It is based upon photolysis of aqueous 2-nitrobenzaldehyde solution, a well-characterized reaction that has been previously demonstrated to be useful as an accurate and reliable actinometric method. Our new method...

article

Formation of fluorescent pyrazine derivatives via a novel degradation pathway of the carbacephalosporin loracarbef

Steven W. Baertschi, Douglas E. Dorman, Larry A. Spangle, Monte W. Collins, more

Journal of Pharmaceutical and Biomedical Analysis > 1995 > 13 > 3 > 323-328

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Search results for: Steven W. Baertschi

Artifactual degradation of secondary amine-containing drugs during accelerated stability testing when saturated sodium nitrite solutions are used for humidity control

Formation of copper(I) from trace levels of copper(II) as an artifactual impurity in the HPLC analysis of olanzapine

Forced Degradation and Its Relation to Real Time Drug Product Stability

Artifacts Generated During Azoalkane Peroxy Radical Oxidative Stress Testing of Pharmaceuticals Containing Primary and Secondary Amines

Implications of In‐Use Photostability: Proposed Guidance for Photostability Testing and Labeling to Support the Administration of Photosensitive Pharmaceutical Products, Part 2: Topical Drug Product

Investigation of the Mechanism of Racemization of Litronesib in Aqueous Solution: Unexpected Base‐Catalyzed Inversion of a Fully Substituted Carbon Chiral Center

Recent Trends in Product Development and Regulatory Issues on Impurities in Active Pharmaceutical Ingredient (API) and Drug Products. Part 2: Safety Considerations of Impurities in Pharmaceutical Products and Surveying the Impurity Landscape

Recent Trends in Product Development and Regulatory Issues on Impurities in Active Pharmaceutical Ingredient (API) and Drug Products. Part 1: Predicting Degradation Related Impurities and Impurity Considerations for Pharmaceutical Dosage Forms

On-column nitrosation of amines observed in liquid chromatography impurity separations employing ammonium hydroxide and acetonitrile as mobile phase

Implications of In‐Use Photostability: Proposed Guidance for Photostability Testing and Labeling to Support the Administration of Photosensitive Pharmaceutical Products, Part 1: Drug Products Administered by Injection

Assessing mass balance in pharmaceutical drug products: New insights into an old topic

The role of analytical chemistry in drug-stability studies

The assessment of impurities for genotoxic potential and subsequent control in drug substance and drug product

Prediction of Drug Degradation Pathways leading to Structural Alerts for Potential Genotoxic Impurities

A critical assessment of the ICH guideline on photostability testing of new drug substances and products (Q1B): Recommendation for revision

Analytical methodologies for discovering and profiling degradation-related impurities

2-Nitrobenzaldehyde: a convenient UV-A and UV-B chemical actinometer for drug photostability testing

Formation of fluorescent pyrazine derivatives via a novel degradation pathway of the carbacephalosporin loracarbef

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