Publications by authors named "Scott Reuschel"

16 Publications

  • Page 1 of 1

GCC Consolidated Feedback to ICH on the 2019 ICH M10 Bioanalytical Method Validation Draft Guideline.

Bioanalysis 2019 Sep 30;11(18s):1-228. Epub 2019 Sep 30.

WuXi Apptec, Shanghai, China.

The 13 GCC Closed Forum for Bioanalysis was held in New Orleans, Louisiana, USA on April 5, 2019. This GCC meeting was organized to discuss the contents of the 2019 ICH M10 Bioanalytical Method Validation Draft Guideline published in February 2019 and consolidate the feedback of the GCC members. In attendance were 63 senior-level participants from eight countries representing 44 bioanalytical CRO companies/sites. This event represented a unique opportunity for CRO bioanalytical experts to share their opinions and concerns regarding the ICH M10 Bioanalytical Method Validation Draft Guideline and to build unified comments to be provided to the ICH.
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http://dx.doi.org/10.4155/bio-2019-0207DOI Listing
September 2019

Quantitative determination of AVI-7100 (Radavirsen), a phosphorodiamidate morpholino oligomer (PMOplus ), in human plasma using LC-MS/MS.

Bioanalysis 2017 May 18;9(10):827-839. Epub 2017 May 18.

Sarepta Therapeutics Incorporated.

Aim: AVI-7100 (Radavirsen) is a 20-mer phosphorodiamidate morpholino oligomer (PMOplus®) for the treatment of influenza. Results/methodology: An automated solid-phase extraction method was used to extract plasma samples (200 μl). The extracts were analyzed using liquid chromatography coupled with tandem mass spectrometry under the positive ionization mode. This method was fully validated over the calibration curve range of 5.00-1000 ng/ml. The between-run precision and accuracy ranged from 0.0 to 5.2% relative standard deviation and 91.6 to 100.0% of nominal for all quality control concentrations, including the lower limit of quantitation.

Discussion/conclusion: This is the first liquid chromatography coupled with tandem mass spectrometry method for the measurement of AVI-7100 concentrations in human plasma. It has been used to support regulated bioanalysis.
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http://dx.doi.org/10.4155/bio-2016-0289DOI Listing
May 2017

Simultaneous quantification of loxapine, loxapine N-oxide, amoxapine, 8-hydroxyloxapine and 7-hydroxyloxapine in human plasma using LC-MS/MS.

J Chromatogr B Analyt Technol Biomed Life Sci 2017 Mar 9;1046:87-97. Epub 2017 Jan 9.

Covance Laboratories, Inc., United States.

Loxapine is an antipsychotic medication used for the treatment of schizophrenia. In vivo, loxapine is metabolized to multiple metabolites. A high performance liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the determination of loxapine and 4 of its metabolites, loxapine N-oxide, amoxapine (N-desmethyl loxapine), 8-hydroxyloxapine and 7-hydroxyloxapine, in human plasma to support regulated clinical development. During method development, several technical challenges such as poor chromatography, separation of structural isomers, and inadequate sensitivity were met and overcome. The final method utilized micro-elution solid phase extraction (SPE) to extract plasma samples (100μL), and the resulting extracts were analyzed using reversed phase LC-MS/MS using a turbo-ionspray interface in positive ionization mode with selected reaction monitoring (SRM). The method was fully validated according to the current regulatory guidance for bioanalysis over the calibration curve range 0.0500-50.0ng/mL for all analytes using 1/x-weighted linear regression analysis. Based on three separate runs, the between-run precision and inter-day precision for all five analytes at all concentrations, including the LLOQ (lower limit of quantitation) quality control at 0.0500ng/mL, varied from 0.0% to 13.8%, while the accuracy ranged from 86.4% to 109.3% of nominal. The extraction recoveries of loxapine and the four metabolites were above 80%. Various forms of short-term and long-term stability were established in both solutions and matrix, including the stability of loxapine and the four metabolites in human plasma for up to 260days of storage at -20°C. This method has been used to support a regulated clinical study, which included the successful execution of incurred sample reanalysis (ISR) testing. To the best of our knowledge, this is the first published methodology in which these five analytes were quantified with a single extraction and injection.
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http://dx.doi.org/10.1016/j.jchromb.2017.01.007DOI Listing
March 2017

Simultaneous quantitation of polymyxin B1, polymyxin B2 and polymyxin B1-1 in human plasma and treated human urine using solid phase extraction and liquid chromatography-tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2016 Feb 12;1012-1013:23-36. Epub 2016 Jan 12.

Covance, 1121 East 3900 South, Salt Lake City, UT 84124, USA.

Two liquid chromatographic-tandem mass spectrometric (LC-MS/MS) methods have been developed and validated for the quantitative determination of polymyxin B1, polymyxin B2 and polymyxin B1-1 concentrations in human plasma and treated urine. During method development, technical challenges such as the separation of structural isomers polymyxin B1and polymyxin B1-1 and nonspecific binding in urine samples were encountered and overcome. Two automated solid phase extraction methods were used to extract plasma samples (100μL) and urine samples (200μL) and the resulting extracts were analyzed using reversed phase LC-MS/MS with an electrospray (ESI) interface and selected reaction monitoring (SRM) in the positive ionization mode. Both methods were validated over a calibration curve range of 5.00-2000ng/mL with a linear regression and 1/x(2) weighting. The between-run relative standard deviation (%RSD) ranged from 4.5 to 9.5% for the plasma assay and from 1.1 to 7.1% for the urine assay. For the plasma assay, the between-run accuracy ranged from 100.5 to 115.2% of nominal at all QC concentrations including the LLOQ. For the urine assay, the between-run accuracy ranged from 92.0 to 106% of nominal at all QC concentrations including the LLOQ. The extraction recoveries for all polymyxins in both assays were between 54.0 and 64.2%. Long term matrix storage stability for all polymyxins was established at both -20°C and -70°C for up to 85 days in human plasma and for up to 55 days in treated human urine. Both assays were used for the measurement of polymyxin B1, polymyxin B2 and polymyxin B1-1 concentrations in human plasma and treated urine for the determination of bioequivalence and toxicokinetic parameters in clinical studies.
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http://dx.doi.org/10.1016/j.jchromb.2016.01.013DOI Listing
February 2016

Determination of GDC-0980 (apitolisib), a small molecule dual phosphatidylinositide 3-kinase/mammalian target of rapamycin inhibitor in dog plasma by LC-MS/MS to support a GLP toxicology study.

Biomed Chromatogr 2015 Aug 10;29(8):1274-9. Epub 2015 Feb 10.

Genentech, Drug Metabolism and Pharmacokinetics, MS 41-2A, 1 DNA Way, South San Francisco, CA, 94080, USA.

An LC-MS/MS method for the determination of GDC-0980 (apitolisib) concentrations in dog plasma has been developed and validated for the first time to support pre-clinical drug development. Following protein precipitation with acetonitrile, the resulting samples were analyzed using reverse-phase chromatography on a Metasil AQ column. The mass analysis was performed on a triple quadruple mass spectrometer coupled with an electrospray interface in positive ionization mode. The selected reaction monitoring transitions monitored were m/z 499.3 → 341.1 for GDC-0980 and m/z 507.3 → 341.1 for IS. The method was validated over the calibration curve range 0.250-250 ng/mL with linear regression and 1/x(2) weighting. Relative standard deviation (RSD) ranged from 0.0 to 10.9% and accuracy ranged from 93.4 to 113.6% of nominal. Stable-labeled internal standard GDC-0980-d8 was used to minimize matrix effects. This assay was used for the measurement of GDC-0980 dog plasma concentrations to determine toxicokinetic parameters after oral administration of GDC-0980 (0.03, 0.1 and 0.3 mg/kg) to beagle dogs in a GLP toxicology study. Peak concentration ranged from 3.23 to 84.9 ng/mL. GDC-0980 was rapidly absorbed with a mean time to peak concentration ranging from 1.3 to 2.4 h. Mean area under the concentration-time curve from 0 to 24 hours ranged from 54.4 to 542 ng h/mL.
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http://dx.doi.org/10.1002/bmc.3417DOI Listing
August 2015

8th GCC: consolidated feedback to US FDA on the 2013 draft FDA guidance on bioanalytical method validation.

Bioanalysis 2014 ;6(22):2957-63

Covance Laboratories, Chantilly, VA, USA.

The 8th GCC Closed Forum for Bioanalysis was held in Baltimore, MD, USA on 5 December 2013, immediately following the 2013 AAPS Workshop (Crystal City V): Quantitative Bioanalytical Methods Validation and Implementation--The 2013 Revised FDA Guidance. This GCC meeting was organized to discuss the contents of the draft revised FDA Guidance on bioanalytical method validation that was published in September 2013 and consolidate the feedback of the GCC members. In attendance were 63 senior-level participants, from seven countries, representing 46 bioanalytical CRO companies/sites. This event represented a unique opportunity for CRO bioanalytical experts to share their opinions and concerns regarding the draft FDA Guidance, and to build unified comments to be provided to the FDA.
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http://dx.doi.org/10.4155/bio.14.287DOI Listing
July 2015

Recommendations on incurred sample stability (ISS) by GCC.

Bioanalysis 2014 Sep;6(18):2385-90

Quintiles Bioanalytical & ADME Labs, Ithaca, NY, USA.

The topic of incurred sample stability (ISS) has generated considerable discussion within the bioanalytical community in recent years. The subject was an integral part of the seventh annual Workshop on Recent Issues in Bioanalysis (WRIB) held in Long Beach, CA, USA, in April 2013, and at the Global CRO Council for Bioanalysis (GCC) meeting preceding it. Discussion at both events focused on the use of incurred samples for ISS purposes in light of results from a recent GCC survey completed by member companies. This paper reports the consensus resulting from these discussions and serves as a useful reference for depicting ISS issues and concerns, summarizing the GCC survey results and providing helpful recommendations on ISS in the context of bioanalytical method development and application.
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http://dx.doi.org/10.4155/bio.14.155DOI Listing
September 2014

Small molecule specific run acceptance, specific assay operation, and chromatographic run quality assessment: recommendation for best practices and harmonization from the global bioanalysis consortium harmonization teams.

AAPS J 2014 Sep 25;16(5):885-93. Epub 2014 Jun 25.

Merck Research Laboratories, WP 75B-300, West Point, Pennsylvania, 19486, USA,

Consensus practices and regulatory guidance for liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) assays of small molecules are more aligned globally than for any of the other bioanalytical techniques addressed by the Global Bioanalysis Consortium. The three Global Bioanalysis Consortium Harmonization Teams provide recommendations and best practices for areas not yet addressed fully by guidances and consensus for small molecule bioanalysis. Recommendations from all three teams are combined in this report for chromatographic run quality, validation, and sample analysis run acceptance.
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http://dx.doi.org/10.1208/s12248-014-9633-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147057PMC
September 2014

Regulated bioanalysis of oligonucleotide therapeutics and biomarkers: qPCR versus chromatographic assays.

Bioanalysis 2013 Nov;5(22):2747-51

Tandem Labs, 1121 East 3900 South, Building C, Suite 105, Salt Lake City, UT 84124, USA.

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http://dx.doi.org/10.4155/bio.13.234DOI Listing
November 2013

Method development and validation of six bile acids for regulated bioanalysis: improving selectivity and sensitivity.

Bioanalysis 2013 May;5(10):1229-48

Tandem Labs, Salt Lake City, UT, USA.

Background: Quantification of bile acids using LC-MS has previously been very challenging on triple quadrupole MS systems due to the absence of a primary fragment ion for unconjugated bile acids.

Results: A LC-high-resolution/accurate mass MS method for the analysis of six bile acids (cholic acid, chenodeoxycholic acid, taurocholic acid, deoxycholic acid, lithocholic acid and ursodeoxycholic acid) was developed and successfully validated. The method includes a single extraction and a single injection with all analytes separated using target-selected ion monitoring (SIM) mode in two periods with a resolution of 70,000 and 140,000, respectively.

Conclusion: This is the first LC-high-resolution/accurate mass assay fully validated to quantify six bile acids for regulated bioanalysis.
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http://dx.doi.org/10.4155/bio.13.94DOI Listing
May 2013

A systematic approach for developing a robust LC-MS/MS method for bioanalysis.

Bioanalysis 2013 Jan;5(1):91-115

Tandem Labs, Salt Lake City, UT, USA.

In order to meet the drug discovery and development needs of pharmaceutical companies, CROs are constantly challenged by the requirements for rapid LC-MS/MS method development prior to method validation and sample analysis. In order to meet this challenge, a comprehensive method development program, nicknamed 'Amoeba™', which uses a series of written protocols for standardized and efficient method development was developed. In this paper, the genesis of the Amoeba method development program is elucidated in detail and a number of case studies are presented to showcase the execution of the Amoeba method development program. Using this program, the majority of the most critical information regarding the assay can be captured. While the Amoeba program has been proven to be effective, we recognize that the development of a robust bioanalytical method for use in pharmaceutical industry also requires the careful consideration of many critical parameters and the ability to identify and resolve potential issues. The refinement of the assay relies on further evaluation of several critical factors including, but not limited to, internal standard response, matrix effects (phospholipid or nonphospholipid related) and carryover.
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http://dx.doi.org/10.4155/bio.12.295DOI Listing
January 2013

Recommendations on biomarker bioanalytical method validation by GCC.

Bioanalysis 2012 Oct;4(20):2439-46

Quotient Bioresearch, Fordham, UK.

The 5th GCC in Barcelona (Spain) and 6th GCC in San Antonio (TX, USA) events provided a unique opportunity for CRO leaders to openly share opinions and perspectives, and to agree upon recommendations on biomarker bioanalytical method validation.
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http://dx.doi.org/10.4155/bio.12.197DOI Listing
October 2012

Recommendations on bioanalytical method stability implications of co-administered and co-formulated drugs by Global CRO Council for Bioanalysis (GCC).

Bioanalysis 2012 Sep;4(17):2117-26

Advion Bioanalytical Laboratories, Quintiles, NY, USA.

An open letter written by the Global CRO Council for Bioanalysis (GCC) describing the GCC survey results on stability data from co-administered and co-formulated drugs was sent to multiple regulatory authorities on 14 December 2011. This letter and further discussions at different GCC meetings led to subsequent recommendations on this topic of widespread interest within the bioanalytical community over the past 2 years.
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http://dx.doi.org/10.4155/bio.12.192DOI Listing
September 2012

Identifying trends and developing solutions for incurred sample reanalysis failure investigations in a bioanalytical CRO.

Bioanalysis 2011 Feb;3(4):449-65

Tandem Labs, Salt Lake City, UT, USA.

In 2007, the US FDA recommended that pharmaceutical companies and CROs conduct incurred sample reanalysis (ISR) following the analysis of study samples using validated methods. Between January 2008 and December 2009, over 250 separate analytes were tested for ISR in our laboratory (a bioanalytical CRO). Among these, nine analytes initially failed for ISR. While thorough investigations were conducted to identify the root cause of ISR failure for each study, these investigations were often painfully tedious and very costly, both financially and in terms of project timelines. In this paper, three representative studies are presented to showcase the detailed investigation processes, methodologies and final conclusions of the ISR investigations. Additionally, all nine ISR failures are analyzed to identify trends or common elements of the studies or methods that might help identify potential problems before they occur. Furthermore, suggestions and recommendations to minimize future ISR failures are provided.
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http://dx.doi.org/10.4155/bio.10.212DOI Listing
February 2011