Development of ESI-LC-MS Method for Drug Analysis

Brain cancer, particularly astrocytomas, is one of the ten most common related deaths related to cancer. Temozolomide (TMZ), an oral alkylating chemotherapy drug, is used to treat anaplastic astrocytoma and glioblastoma multiforme. A few advantages of TMZ are its ability to cross the blood-brain barrier, its small size, and it is rapidly absorbed in the small intestine. Since this drug is advantageous to brain cancer patients, it is important to study the extraction of this drug. In addition, it is important to study administering this drug via microdialysis as the efficiency of the drug could increase. In mice brain tumor tissue and lamb brain tissue, LC-MS was used to quantitate TMZ. TMZ has been recovered from brain tissue using a strong cell lysis protease (proteinase K) and protein precipitation using alcohol dehydration in order to increase percent recovery of TMZ and decrease matrix effects. Most research articles have studied the plasma or urine of mice to quantitate TMZ. However, only a handful of studies focused on brain tumor tissue. Comparing with another research article that studied the recovery of TMZ from mice brain tissue, this method achieved higher percent recoveries of the chemotherapy drug, and lowered the matrix effects

Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Temozolomide in Mouse Brain Tissue

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

Development of ESI-LC-MS Method for Drug Analysis

Brain cancer, particularly astrocytomas, is one of the ten most common related deaths related to cancer. Temozolomide (TMZ), an oral alkylating chemotherapy drug, is used to treat anaplastic astrocytoma and glioblastoma multiforme. A few advantages of TMZ are its ability to cross the blood-brain barrier, its small size, and it is rapidly absorbed in the small intestine. Since this drug is advantageous to brain cancer patients, it is important to study the extraction of this drug. In addition, it is important to study administering this drug via microdialysis as the efficiency of the drug could increase. In mice brain tumor tissue and lamb brain tissue, LC-MS was used to quantitate TMZ. TMZ has been recovered from brain tissue using a strong cell lysis protease (proteinase K) and protein precipitation using alcohol dehydration in order to increase percent recovery of TMZ and decrease matrix effects. Most research articles have studied the plasma or urine of mice to quantitate TMZ. However, only a handful of studies focused on brain tumor tissue. Comparing with another research article that studied the recovery of TMZ from mice brain tissue, this method achieved higher percent recoveries of the chemotherapy drug, and lowered the matrix effects

Development of ESI-LC-MS Method for Drug Analysis

Brain cancer, particularly astrocytomas, is one of the ten most common related deaths related to cancer. Temozolomide (TMZ), an oral alkylating chemotherapy drug, is used to treat anaplastic astrocytoma and glioblastoma multiforme. A few advantages of TMZ are its ability to cross the blood-brain barrier, its small size, and it is rapidly absorbed in the small intestine. Since this drug is advantageous to brain cancer patients, it is important to study the extraction of this drug. In addition, it is important to study administering this drug via microdialysis as the efficiency of the drug could increase. In mice brain tumor tissue and lamb brain tissue, LC-MS was used to quantitate TMZ. TMZ has been recovered from brain tissue using a strong cell lysis protease (proteinase K) and protein precipitation using alcohol dehydration in order to increase percent recovery of TMZ and decrease matrix effects. Most research articles have studied the plasma or urine of mice to quantitate TMZ. However, only a handful of studies focused on brain tumor tissue. Comparing with another research article that studied the recovery of TMZ from mice brain tissue, this method achieved higher percent recoveries of the chemotherapy drug, and lowered the matrix effects