Rapid Determination of Pemetrexed Concentration and Distribution in Human Breast Cancer Cells (McF-7) Based on UHPLC-MS/MS
Cell is the basic unit of structure and function of all living bodies. The study of intracellular drug concentration distribution is helpful to understand the drug efficacy of target site. Pemetrexed is a new multitarget folate antagonist with pyrrolidine group as its core structure. An ultra high-p...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | International Journal of Analytical Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2021/6614332 |
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| author | Mengwei Zhang Zhipeng Wang Qiqiang Zhang Qing Ye Fengjing Xu Lili Cui Yanping Liu Shouhong Gao Wansheng Chen Yan Liu |
| author_facet | Mengwei Zhang Zhipeng Wang Qiqiang Zhang Qing Ye Fengjing Xu Lili Cui Yanping Liu Shouhong Gao Wansheng Chen Yan Liu |
| author_sort | Mengwei Zhang |
| collection | DOAJ |
| description | Cell is the basic unit of structure and function of all living bodies. The study of intracellular drug concentration distribution is helpful to understand the drug efficacy of target site. Pemetrexed is a new multitarget folate antagonist with pyrrolidine group as its core structure. An ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed for rapid quantification of pemetrexed concentration in human breast cancer cells (MCF-7). Sample pretreatment was completed by protein precipitation using methanol. The optimized chromatographic separation was achieved on a ZORBAX SB-C18 column (2.1 × 150 mm, 3.5 μm). The column was equilibrated with initial mobile phase and eluted under gradient phases containing 0.1% formic acid in water (phase A) and in acetonitrile (phase B). The gradient program started at 5% B, increased to 95% B in 2 min, and then held at 95% B for 1.5 min. The linear range of pemetrexed in cells and nucleus was 2.0–200.0 ng/mL, while in the medium sample it was 50.0–5000.0 ng/ml, and the correlation coefficients were all greater than 0.99. The recovery was 47.50–67.55% (2.0–200.0 ng/mL) and 82.72–97.15% (50.0–5000.0 ng/mL), and the matrix effect was 98.10–100.62% (2.0–200.0 ng/mL) and 89.78–97.65% (50.0–5000.0 ng/mL). Interday precision and intraday precision (RSD%) were less than 15.0% (for LLOQ, less than 20%), and accuracy (RE%) was within ±15%; the deviation of stability was within ±15%, all meeting the requirements of biological sample analysis. The results of intracellular samples showed that the concentration of pemetrexed reached its peak at 3 h after administration. The concentration of pemetrexed in the nucleus continued to increase 2 h after administration and may have reached the maximum concentration at 6 h. |
| format | Article |
| id | doaj-art-6749fde9e3a14dccafee915681044b4d |
| institution | Kabale University |
| issn | 1687-8760 1687-8779 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Analytical Chemistry |
| spelling | doaj-art-6749fde9e3a14dccafee915681044b4d2025-02-03T06:06:28ZengWileyInternational Journal of Analytical Chemistry1687-87601687-87792021-01-01202110.1155/2021/66143326614332Rapid Determination of Pemetrexed Concentration and Distribution in Human Breast Cancer Cells (McF-7) Based on UHPLC-MS/MSMengwei Zhang0Zhipeng Wang1Qiqiang Zhang2Qing Ye3Fengjing Xu4Lili Cui5Yanping Liu6Shouhong Gao7Wansheng Chen8Yan Liu9Department of Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaDepartment of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, ChinaDepartment of Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaDepartment of Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaDepartment of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, ChinaDepartment of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, ChinaDepartment of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, ChinaDepartment of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, ChinaDepartment of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, ChinaDepartment of Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaCell is the basic unit of structure and function of all living bodies. The study of intracellular drug concentration distribution is helpful to understand the drug efficacy of target site. Pemetrexed is a new multitarget folate antagonist with pyrrolidine group as its core structure. An ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed for rapid quantification of pemetrexed concentration in human breast cancer cells (MCF-7). Sample pretreatment was completed by protein precipitation using methanol. The optimized chromatographic separation was achieved on a ZORBAX SB-C18 column (2.1 × 150 mm, 3.5 μm). The column was equilibrated with initial mobile phase and eluted under gradient phases containing 0.1% formic acid in water (phase A) and in acetonitrile (phase B). The gradient program started at 5% B, increased to 95% B in 2 min, and then held at 95% B for 1.5 min. The linear range of pemetrexed in cells and nucleus was 2.0–200.0 ng/mL, while in the medium sample it was 50.0–5000.0 ng/ml, and the correlation coefficients were all greater than 0.99. The recovery was 47.50–67.55% (2.0–200.0 ng/mL) and 82.72–97.15% (50.0–5000.0 ng/mL), and the matrix effect was 98.10–100.62% (2.0–200.0 ng/mL) and 89.78–97.65% (50.0–5000.0 ng/mL). Interday precision and intraday precision (RSD%) were less than 15.0% (for LLOQ, less than 20%), and accuracy (RE%) was within ±15%; the deviation of stability was within ±15%, all meeting the requirements of biological sample analysis. The results of intracellular samples showed that the concentration of pemetrexed reached its peak at 3 h after administration. The concentration of pemetrexed in the nucleus continued to increase 2 h after administration and may have reached the maximum concentration at 6 h.http://dx.doi.org/10.1155/2021/6614332 |
| spellingShingle | Mengwei Zhang Zhipeng Wang Qiqiang Zhang Qing Ye Fengjing Xu Lili Cui Yanping Liu Shouhong Gao Wansheng Chen Yan Liu Rapid Determination of Pemetrexed Concentration and Distribution in Human Breast Cancer Cells (McF-7) Based on UHPLC-MS/MS International Journal of Analytical Chemistry |
| title | Rapid Determination of Pemetrexed Concentration and Distribution in Human Breast Cancer Cells (McF-7) Based on UHPLC-MS/MS |
| title_full | Rapid Determination of Pemetrexed Concentration and Distribution in Human Breast Cancer Cells (McF-7) Based on UHPLC-MS/MS |
| title_fullStr | Rapid Determination of Pemetrexed Concentration and Distribution in Human Breast Cancer Cells (McF-7) Based on UHPLC-MS/MS |
| title_full_unstemmed | Rapid Determination of Pemetrexed Concentration and Distribution in Human Breast Cancer Cells (McF-7) Based on UHPLC-MS/MS |
| title_short | Rapid Determination of Pemetrexed Concentration and Distribution in Human Breast Cancer Cells (McF-7) Based on UHPLC-MS/MS |
| title_sort | rapid determination of pemetrexed concentration and distribution in human breast cancer cells mcf 7 based on uhplc ms ms |
| url | http://dx.doi.org/10.1155/2021/6614332 |
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