Publications by authors named "Daniel Mulvana"

6 Publications

  • Page 1 of 1

LC-MS/MS quantification of asymmetric dimethyl arginine and symmetric dimethyl arginine in plasma using surrogate matrix and derivatization with fluorescamine.

Bioanalysis 2020 Nov 5;12(22):1607-1619. Epub 2020 Nov 5.

Q Solutions, 19 Brown Road, Ithaca, NY 14850, USA.

A novel LC-MS/MS method using a surrogate matrix and derivatization with fluorescamine was developed and validated for simultaneous quantification of asymmetric dimethyl arginine and symmetric dimethyl arginine. Asymmetric dimethyl arginine, symmetric dimethyl arginine and corresponding internal standards were extracted using protein precipitation and derivatization with fluorescamine followed by SPE. Derivatives were analyzed by turbo ion spray LC-MS/MS in the positive ion mode. Methodology was successfully transferred across multiple preclinical species and utilized in the support of several investigative studies. A new LC-MS/MS analytical methodology that utilizes a surrogate matrix and derivatization with fluorescamine was successfully developed and validated.
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http://dx.doi.org/10.4155/bio-2020-0223DOI Listing
November 2020

HRMS using a Q-Exactive series mass spectrometer for regulated quantitative bioanalysis: how, when, and why to implement.

Bioanalysis 2016 Aug 27;8(16):1709-21. Epub 2016 Jul 27.

Q2 Solutions, 19 Brown Road, Ithaca, NY 14850, USA.

High-resolution MS (HRMS) has seen an uptake in use for discovery qual/quan workflows, however, its utilization in late discovery/development has been slow. Past reports comparing HRMS to triple quadrupole (QQQ) instrumentation to date have indicated that HRMS instruments are capable of producing data acceptable for regulated bioanalysis, however lack the sensitivity required for sub ng/ml LLOQ assays. Recent advances in HRMS instrumentation have closed the sensitivity gap with QQQ and have even provided improved selectivity and sensitivity over QQQ SRM assays. Herein, the authors will describe how, when, and why HRMS (specifically Q-Exactive series mass spectrometers) should be considered for implementation in regulated quantitative bioanalysis assays.
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http://dx.doi.org/10.4155/bio-2016-0079DOI Listing
August 2016

9th GCC closed forum: CAPA in regulated bioanalysis; method robustness, biosimilars, preclinical method validation, endogenous biomarkers, whole blood stability, regulatory audit experiences and electronic laboratory notebooks.

Bioanalysis 2016 Mar 26;8(6):487-95. Epub 2016 Feb 26.

WuXi/XBL, 107 Morgan Lane, Plainsboro, NJ, USA.

The 9th GCCClosed Forum was held just prior to the 2015 Workshop on Recent Issues in Bioanalysis (WRIB) in Miami, FL, USA on 13 April 2015. In attendance were 58 senior-level participants, from eight countries, representing 38 CRO companies offering bioanalytical services. The objective of this meeting was for CRO bioanalytical representatives to meet and discuss scientific and regulatory issues specific to bioanalysis. The issues selected at this year's closed forum include CAPA, biosimilars, preclinical method validation, endogenous biomarkers, whole blood stability, and ELNs. A summary of the industry's best practices and the conclusions from the discussion of these topics is included in this meeting report.
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http://dx.doi.org/10.4155/bio.16.16DOI Listing
March 2016

Development of a sensitive and fast UHPLC-MS/MS method for determination of clopidogrel, clopidogrel acid and clopidogrel active metabolite H4 in human plasma.

Bioanalysis 2015 ;7(12):1471-82

Bioanalytical & ADME Labs, Quintiles, Ithaca, NY 14850, USA.

Background: Quantitation of CAM H4 in biological matrix has been a challenge due to low concentrations, instability and the existence of four CAM diastereomers. Historically, either inactive clopidogrel acid or CAM diastereomers without separation were measured for exposure and PK parameters.

Results: This study presents a sensitive and fast UHPLC-MS/MS method for simultaneous quantitation of clopidogrel, clopidogrel acid and active metabolite H4 in human plasma. The method demonstrated the separation of H4 from other isomers and yet retained clopidogrel acid. Matrix stabilities, accuracy and precision, recovery and matrix effect were evaluated during development.

Conclusion: With LLOQ of 0.05 ng/ml for clopidogrel and H4, and 5.5 min LC gradient, it is the most sensitive and fastest method to our knowledge.
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http://dx.doi.org/10.4155/bio.15.82DOI Listing
April 2016

Development and validation of a HILIC-MS/MS method for quantification of decitabine in human plasma by using lithium adduct detection.

J Chromatogr B Analyt Technol Biomed Life Sci 2014 Oct 15;969:117-22. Epub 2014 Aug 15.

Bioanalytical and ADME Labs, Quintiles, 19 Brown Road, Ithaca, NY 14850, USA.

A highly sensitive, selective, and rugged quantification method was developed and validated for decitabine (5-aza-2'-deoxycytidine) in human plasma treated with 100μg/mL of tetrahydrouridine (THU). Chromatographic separation was accomplished using hydrophilic interaction liquid chromatography (HILIC) and detection used electrospray ionization (ESI) tandem mass spectrometry (MS/MS) by monitoring lithiated adducts of the analytes as precursor ions. The method involves simple acetonitrile precipitation steps (in an ice bath) followed by injection of the supernatant onto a Thermo Betasil Silica-100, 100×3.0mm, 5μm LC column. Protonated ([M+H](+)), sodiated ([M+Na](+)), and lithiated ([M+Li](+)) adducts as precursor ions for MS/MS detection were evaluated for best sensitivity and assay performance. During initial method development abundant sodium [M+Na](+) and potassium [M+K](+) adducts were observed while the protonated species [M+H](+) was present at a relative abundance of less than 5% in Q1. The alkali adducts were not be able to be minimized by the usual approach of increasing acid content in mobile phases. Significant analyte/internal standard (IS) co-suppression and inter-lot response differences were observed when using the sodium adduct as the precursor ion for quantification. By adding 2mM lithium acetate in aqueous mobile phase component, the lithium adduct effectively replaced other cationic species and was successfully used as the precursor ion for selected reaction monitoring (SRM) detection. The method demonstrated the separation of anomers and from other endogenous interferences using a 3-min gradient elution. Decitabine stock, working solution stabilities were investigated during method development. Three different peaks, including one from anomerization, were observed in the SRM transition of the analyte when it was in neutral aqueous solution. The assay was validated over a concentration range of 0.5-500ng/mL (or 0.44-440pg injected on column) in 50μL of human plasma. The accuracy and precision were within 8.6% relative error and 6.3% coefficient of variation, respectively. Decitabine was stable in THU treated human plasma for at least 68 days and after 5 freeze-thaw cycles when stored at -70°C. Stability of decitabine in THU treated human whole blood, matrix factor and recovery were also evaluated during method validation. The method was successfully used for clinical sample analysis.
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http://dx.doi.org/10.1016/j.jchromb.2014.08.012DOI Listing
October 2014

Critical topics in ensuring data quality in bioanalytical LC-MS method development.

Authors:
Daniel E Mulvana

Bioanalysis 2010 Jun;2(6):1051-72

Advion BioSciences, Ithaca, NY, USA.

The use of LC-MS for bioanalysis of pharmaceuticals is entering its third decade and may be considered to be a mature technology. In many respects this is true, considering the advances made in such areas as instrument performance, electronics, software and automation of use. However, there remain instrumental and noninstrumental areas that require significant attention to ensure data quality. Increasing regulatory focus on analytical method performance and unaddressed method issues require the bioanalyst to understand those areas that most greatly impact data quality. This review will focus on instrumental and noninstrumental areas that can influence data quality, including reference standard and internal standard quality and physicochemical properties, matrix effects, stability in matrix, sample preparation, LC and MS.
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http://dx.doi.org/10.4155/bio.10.60DOI Listing
June 2010