TY - JOUR
T1 - Using differential mobility spectrometry to improve the specificity of targeted measurements of 2,3-dinor 11β-Prostaglandin F2α
AU - Moehnke, Kayla
AU - Kemp, Jennifer
AU - Campbell, Michelle R.
AU - Singh, Ravinder Jit
AU - Tebo, Anne E.
AU - Maus, Anthony
N1 - Publisher Copyright:
© 2024 The Canadian Society of Clinical Chemists
PY - 2024/4
Y1 - 2024/4
N2 - Introduction: 2,3-dinor 11β-Prostaglandin F2α (BPG) is an arachidonic acid derivative and the most abundant metabolic byproduct of prostaglandin D2, which is released during mast cell activation. Therefore, measurements of BPG in urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS) provide a noninvasive method for evaluation and management of mast cell disorders. Measurements obtained by LC-MS/MS exhibit a high prevalence of chromatographic interferences resulting in challenges with optimal determination of BGP. In this investigation, differential mobility spectrometry (DMS) is utilized to overcome the limitations of current testing. Methods: Urine samples were extracted using an automated solid-phase extraction method. Samples were then analyzed with and without DMS devices installed on two commercially available mass spectrometry platforms to assess the benefits of DMS. Following promising results from a preliminary analytical evaluation, LC-DMS-MS/MS measurements of BPG in urine were fully validated to assess the analytical implications of using this technology. Results and discussion: The addition of DMS devices to the LC-MS/MS systems evaluated in this investigation significantly reduced interferences observed in the chromatograms. Concomitantly, DMS reduced the number of discordant quantifier/qualifier fragment ion results that significantly exceeded the ± 20 % limits, suggesting greater analytical specificity. The validation studies yielded low interday imprecision, with %CVs less than 6.5 % across 20 replicate measurements. Validation studies assessing other aspects of analytical performance also met acceptance criteria. Conclusions: Incorporating DMS devices greatly improved the specificity of BPG measurements by LC-MS/MS, as evidenced by the comparison of chromatograms and fragment ion results. Validation studies showed exceptional performance for established analytical metrics, indicating that this technology can be used to minimize the impact of interferences without adversely impacting other aspects of analytical or clinical performance.
AB - Introduction: 2,3-dinor 11β-Prostaglandin F2α (BPG) is an arachidonic acid derivative and the most abundant metabolic byproduct of prostaglandin D2, which is released during mast cell activation. Therefore, measurements of BPG in urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS) provide a noninvasive method for evaluation and management of mast cell disorders. Measurements obtained by LC-MS/MS exhibit a high prevalence of chromatographic interferences resulting in challenges with optimal determination of BGP. In this investigation, differential mobility spectrometry (DMS) is utilized to overcome the limitations of current testing. Methods: Urine samples were extracted using an automated solid-phase extraction method. Samples were then analyzed with and without DMS devices installed on two commercially available mass spectrometry platforms to assess the benefits of DMS. Following promising results from a preliminary analytical evaluation, LC-DMS-MS/MS measurements of BPG in urine were fully validated to assess the analytical implications of using this technology. Results and discussion: The addition of DMS devices to the LC-MS/MS systems evaluated in this investigation significantly reduced interferences observed in the chromatograms. Concomitantly, DMS reduced the number of discordant quantifier/qualifier fragment ion results that significantly exceeded the ± 20 % limits, suggesting greater analytical specificity. The validation studies yielded low interday imprecision, with %CVs less than 6.5 % across 20 replicate measurements. Validation studies assessing other aspects of analytical performance also met acceptance criteria. Conclusions: Incorporating DMS devices greatly improved the specificity of BPG measurements by LC-MS/MS, as evidenced by the comparison of chromatograms and fragment ion results. Validation studies showed exceptional performance for established analytical metrics, indicating that this technology can be used to minimize the impact of interferences without adversely impacting other aspects of analytical or clinical performance.
KW - Differential mobility spectrometry
KW - Ion mobility
KW - LC-MS/MS
KW - Tandem mass spectrometry
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U2 - 10.1016/j.clinbiochem.2024.110745
DO - 10.1016/j.clinbiochem.2024.110745
M3 - Article
C2 - 38462204
AN - SCOPUS:85187314920
SN - 0009-9120
VL - 126
JO - Clinical Biochemistry
JF - Clinical Biochemistry
M1 - 110745
ER -