Performance Comparison of Liquid Chromatography and Paper Spray Ionization with Mass Spectrometry for Measuring Kinase Inhibitors in Human Plasma

ACS Pharmacology & Translational Science, Journal Year: 2025, Volume and Issue: 8(2), P. 557 - 565

Published: Jan. 16, 2025

Kinase inhibitors are small-molecule drugs designed to target oncogenic mutations in cancer treatment. Although less toxic than conventional chemotherapy drugs, they can cause severe adverse effects some patients, resulting dose reduction and cessation. To evaluate if therapeutic drug monitoring of kinase their metabolites improve toxicity assessment we developed evaluated the analytical performance two parallel methods utilizing liquid chromatography (LC) paper spray (PS) ionization coupled with a triple quadrupole mass spectrometer (MS) for measurement dabrafenib, its major metabolite OH-dabrafenib, trametinib patient plasma samples. The PS-MS method yielded faster sample analysis time (2 min) compared LC separation (9 min). shared same range (AMR) dabrafenib OH-dabrafenib (10-3500 10-1250 ng/mL), but AMR differed (LC-MS: 0.5-50 ng/mL; PS-MS: 5.0-50 ng/mL). imprecision across respective was 1.3-6.5% (dabrafenib), 3.0-9.7% (OH-dabrafenib), 1.3-5.1% (trametinib) LC-MS 3.8-6.7% 4.0-8.9% 3.2-9.9% method. Using authentic samples, quantification results were comparable between methods: (correlation coefficient r = 0.9977), (r 0.885), 0.9807). Nonetheless, displayed significantly higher variations Based on method, able profile concentrations metabolism patterns patients who receiving BRAF V600 mutation-driven malignancies.

Language: Английский

Identification and Mitigation of Pyrolysis Products in Laser-Cut Paper for Paper Spray Mass Spectrometry

Journal of the American Society for Mass Spectrometry, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Paper spray mass spectrometry (PS-MS) often employs laser cutting to prepare paper substrates, potentially inducing localized thermal decomposition of the cellulose backbone. This work investigates how pyrolysis products and inherent background molecules within affect PS-MS signal quality evaluates pretreatment methods enhance performance. Comparative analyses laser-cut razor-cut using ultraviolet-visible spectroscopy (UV-vis) showed significant differences. Laser-cut exhibited elevated MS blank signals higher absorbance in 200-400 nm UV region, indicating increased chemical abundance complexity. Gas chromatography-mass (GC-MS) identified over 20 residual compounds on absent samples, half which were as known products. Washing substrates with methanol, water, or dilute nitric acid significantly reduced both molecules, water showing most improvement. Analyses morphine, fentanyl, methamphetamine, voriconazole, fluconazole no reduction after washing, fentanyl methamphetamine exhibiting a signal, regardless method. reveals that while from contribute noise, also play role. A simple wash mitigates issues, improving overall performance for range analytes.

Language: Английский

Internal Standard Utilization Strategies for Quantitative Paper Spray Mass Spectrometry

Journal of the American Society for Mass Spectrometry, Journal Year: 2025, Volume and Issue: unknown

Published: April 5, 2025

Premixing internal standards (ISTD) with liquid samples prior to paper spray mass spectrometry (PS-MS) analysis consumes unnecessary amounts of ISTD and is not feasible for all sample types applications. Depositing directly on the independently from has been successfully employed in literature but can negatively affect quantitative performance. We evaluated different utilization strategies using drugs misuse as test analytes investigate sources irreproducibility bias. Performance was assessed both pre- postdeposited (relative loading) at volumes a constant final loading 1 ng each compound. Precision accuracy were lower when deposited compared premixed (average CV = 18% vs 1% average |bias| 61% 5% ISTD, respectively). The use robotic handling system deposit results obtained via manually pipetting. Predeposited performed best deposition handler used 8% 11% 2 10 μL, respectively), manual pipetting low volume depositions poorly. Postdeposited inferior predeposited strategies, favoring larger regardless method 22% 16% Systematic biases associated strategy effectively corrected strategy-matched calibrations, AAFS (American Academy Forensic Sciences) precision requirements achieved almost cases.

Language: Английский