Separation Science Plus
Temozolomide is a Food and Drug Administration-approved anticancer drug that has poor drug delivery via oral or intravenous routes. A potential strategy to combat this problem is investigating alternative routes of administration, requiring quantitation of the drug in the brain tissues by liquid chromatography-mass spectrometry. However, current methods used to extract the drug from brain tissues resulted in poor recovery and substantial matrix effects. Herein, we reported a new two-step extraction method that involves the use of Proteinase K to lyse tumor tissues to efficiently release the drug, followed by ethanol protein precipitation. The extracts were then separated on a C18 column and analyzed in positive electrospray ionization, a multiple reaction monitoring mode of the triple quadrupole. We found this new method led to a recovery of 82% with negligible matrix effects. The method has been validated in accordance with Food and Drug Administration guidance for linearity, specificity, selectivity, accuracy, precision, carry-over, stability, and lower limit of quantitation. In conclusion, we have developed and validated a liquid chromatography-mass spectrometry method with a novel sample preparation method that was able to efficiently extract temozolomide from mouse brain tissue with high recovery.
Kakarla, Raghavi; Yacoub, Kimberly; Bearden, Rebecca L.; Zhou, Aimin; Mukherjee, Sanjib; Shan, Frank Y.; and Guo, Baochuan, "Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Temozolomide in Mouse Brain Tissue" (2023). Chemistry Faculty Publications. 625.
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