LC–MS/MS Used to Detect Colorectal Cancer Drugs in Plasma

Scientists from China Pharmaceutical University in Nanjing, China recent developed a liquid chromatography-tandem mass spectrometry (LC–MS/MS)-based method for determining the presence of anti-colorectal cancer drugs in human plasma. Their findings were published in the Journal of Pharmaceutical and Biomedical Analysis (1).

Colorectal cancer is one of the most common malignant cancers in the world. Starting in the colon or the rectum, most colorectal cancers start as growths on the inner lining of the colon or rectum, with the growths also being known as polyps (2). According to the American Cancer Society, approximately 150,000 cases of CRC will occur in 2024, with approximately 53,010 deaths expected during 2024 (2). Current CRC treatments rely on surgical removal, local treatment, and chemotherapy. However, approximately 50% of patients will develop metastases, where cancer cells spread from the place they first formed to another part of the body. CRC is resistant to traditional chemotherapeutic drugs that can be used for metastatic CRC treatment; as such, additional treatment options must be found for metastatic CRC.

Read More: UHPLC–MS-Based Method Used to Test Potential Colorectal Cancer Treatment

For this study, the scientists created and fully validated a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC–MS/MS) method. This method was created for the simultaneous determination of trifluridine (FTD) and tipiracil (TPI) hydrochloride tablets (TAS-102), which are two medications that can be used to treat colorectal cancer. Using the LC-MS/MS method, the scientists tested for levels of TPI, FTD, and the metabolite 5-trifluoromethyluracil (FTY) of FTD in human plasma. The plasma samples were prepared by protein precipitation, with the chromatographic separation having a gradient elution of 0.05% acetic acid in water and methanol at a flow rate of 0.35 mL/min. The MS/MS analysis was performed by using multiple reaction monitoring with the segmented polarity electrospray ionization mode. This mode was designed to achieve better sensitivity and allow for simultaneous determination of the analytes with different ion polarities.

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The calibration ranges were 1.00–250 ng/mL for TPI, 8.00–8000 ng/mL for FTD, and 5.00–1250 ng/mL for FTY. The electivity, accuracy, precision, matrix effect, recovery, carryover, dilution integrity and stability test results all successfully met ICH acceptance criteria. After the initial procedures, the method was evaluated using the RGB model, one of the most widely used color representation methods in computer graphics (4). From there, it was successfully applied to a clinical study in patients with solid tumors. For TPI, FTD and FTY, the maximum plasma concentration was 137–147 ng/mL, 6160–6240 ng/mL and 724–725 ng/mL, respectively. After an oral administration of 60 mg of TAS-102, the plasma elimination half-life was 1.69–1.78 h, 1.70 h, and 3.09–3.14 h, respectively.

Scientists are also looking into other techniques for treating CRC. For example, a study out of the Chinese Academy of Sciences recently tested using ultrahigh-pressure liquid chromatography–mass spectrometry (UHPLC–MS) to treat colorectal cancer. To learn more about this news story, click here.

References

(1) Zhang, R.; Li, X.; Zhou, Q.; Zhang, X.; Shu, C.; Ding, Li. Simultaneous Determination of Tipiracil, Trifluridine and its Metabolite 5-Trifluoromethyluracil in Human Plasma Using Segmented Polarity LC-MS/MS: A Fully Validated Assay with Clinical Application. J. Pharm. Biomed. Anal. 2024, 239, 115885. DOI: 10.1016/j.jpba.2023.115885

(2) Key Statistics for Colorectal Cancer. American Cancer Society 2024. https://www.cancer.org/cancer/types/colon-rectal-cancer/about/key-statistics.html (accessed 2024-5-1)

(3) Computer Graphics | The RGB Color Model. GeeksforGeeks 2022. https://www.geeksforgeeks.org/computer-graphics-the-rgb-color-model/ (accessed 2024-5-1)