Assessment of Tissue Distribution and Metabolism of MP1, a Novel Pyrrolomycin, in Mice Using a Validated LC-MS/MS Method

MP1 is a novel marinopyrrole analogue with activity in MYCN amplified neuroblastoma cell lines. A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitation of MP1 in mouse plasma. Analyte separation was...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2020-12, Vol.25 (24), p.5898
Main Authors: Aldhafiri, Wafaa N, Chhonker, Yashpal S, Zhang, Yuning, Coutler, Don W, McGuire, Timothy R, Li, Rongshi, Murry, Daryl J
Format: Article
Language:English
Subjects:
Accuracy
Acetic acid
Animals
Autophagy
biodistribution
Cancer
Cell lines
Chromatography
Chromatography, Liquid
Correlation coefficient
Correlation coefficients
Flow velocity
in-vitro metabolism
LC-MS/MS
Liquid chromatography
Mass spectrometry
Mass spectroscopy
Metabolism
Mice
Neuroblastoma
Pediatrics
Plasma
Protein turnover
Proteins
Pyrroles - chemistry
Pyrroles - metabolism
Pyrroles - pharmacokinetics
pyrrolomycin
Quantitation
Reproducibility of Results
Sensitivity and Specificity
Solubility
Tandem Mass Spectrometry
Tissue Distribution
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Summary:MP1 is a novel marinopyrrole analogue with activity in MYCN amplified neuroblastoma cell lines. A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitation of MP1 in mouse plasma. Analyte separation was achieved using a Waters Acquity UPLC BEH C18 column (1.7 µm, 100 × 2.1 mm). Mobile phase consisted of 0.1% acetic acid in water (10%) and methanol (90%) at a total flow rate of 0.25 mL/min. The mass spectrometer was operated at unit resolution in the multiple reaction monitoring (MRM) mode, using precursor ion > product ion transitions of 324.10 > 168.30 / for MP1 and 411.95 > 224.15 / for PL-3. The MS/MS response was linear over the concentration range from 0.2-500 ng/mL for MP1, correlation coefficient (r ) of 0.988. Precision (% RSD) and accuracy (% bias) were within the acceptable limits as per FDA guidelines. MP1 was stable under storage and laboratory handling conditions. The validated method was successfully applied to assess the solubility, in-vitro metabolism, plasma protein binding, and bio-distribution studies of MP1.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules25245898