Development and Validation of a Bioanalytical LC-MS/MS Method for Simultaneous Determination of Sirolimus in Porcine Whole Blood and Lung Tissue and Pharmacokinetic Application with Coronary Stents
Sirolimus is a hydrophobic macrolide compound that has been used for long-term immunosuppressive therapy, prevention of restenosis, and treatment of lymphangioleiomyomatosis. In this study, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated f...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/2/425 |
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| author | Thi-Thao-Linh Nguyen Van-An Duong Dang-Khoa Vo Jeongae Jo Han-Joo Maeng |
| author_facet | Thi-Thao-Linh Nguyen Van-An Duong Dang-Khoa Vo Jeongae Jo Han-Joo Maeng |
| author_sort | Thi-Thao-Linh Nguyen |
| collection | DOAJ |
| description | Sirolimus is a hydrophobic macrolide compound that has been used for long-term immunosuppressive therapy, prevention of restenosis, and treatment of lymphangioleiomyomatosis. In this study, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated for the simultaneous determination of sirolimus in both porcine whole blood and lung tissue. Blood and lung tissue homogenates were deproteinized with acetonitrile and injected into the LC-MS/MS system for analysis using the positive electrospray ionization mode. The drug was separated on a C18 reversed phase column with a gradient mobile phase (ammonium formate buffer (5 mM) with 0.1% formic acid and acetonitrile) at 0.2 mL/min. The selected reaction monitoring transitions of <i>m</i>/<i>z</i> 931.5 → 864.4 and <i>m/z</i> 809.5 → 756.5 were applied for sirolimus and ascomycin (the internal standard, IS), respectively. The method was selective and linear over a concentration range of 0.5–50 ng/mL. The method was validated for sensitivity, accuracy, precision, extraction recovery, matrix effect, and stability in porcine whole blood and lung tissue homogenates, and all values were within acceptable ranges. The method was applied to a pharmacokinetic study to quantitate sirolimus levels in porcine blood and its distribution in lung tissue following the application of stents in the porcine coronary arteries. It enabled the quantification of sirolimus concentration until 2 and 14 days in blood and in lung tissue, respectively. This method would be appropriate for both routine porcine pharmacokinetic and bio-distribution studies of sirolimus formulations. |
| first_indexed | 2024-03-09T04:42:14Z |
| format | Article |
| id | doaj.art-b93428ac491e43f7b0d01ee291e40cba |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T04:42:14Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b93428ac491e43f7b0d01ee291e40cba2023-12-03T13:19:40ZengMDPI AGMolecules1420-30492021-01-0126242510.3390/molecules26020425Development and Validation of a Bioanalytical LC-MS/MS Method for Simultaneous Determination of Sirolimus in Porcine Whole Blood and Lung Tissue and Pharmacokinetic Application with Coronary StentsThi-Thao-Linh Nguyen0Van-An Duong1Dang-Khoa Vo2Jeongae Jo3Han-Joo Maeng4College of Pharmacy, Gachon University, Incheon 21936, KoreaCollege of Pharmacy, Gachon University, Incheon 21936, KoreaCollege of Pharmacy, Gachon University, Incheon 21936, KoreaDepartment of New Drug Development, Inha University College of Medicine, Incheon 22212, KoreaCollege of Pharmacy, Gachon University, Incheon 21936, KoreaSirolimus is a hydrophobic macrolide compound that has been used for long-term immunosuppressive therapy, prevention of restenosis, and treatment of lymphangioleiomyomatosis. In this study, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated for the simultaneous determination of sirolimus in both porcine whole blood and lung tissue. Blood and lung tissue homogenates were deproteinized with acetonitrile and injected into the LC-MS/MS system for analysis using the positive electrospray ionization mode. The drug was separated on a C18 reversed phase column with a gradient mobile phase (ammonium formate buffer (5 mM) with 0.1% formic acid and acetonitrile) at 0.2 mL/min. The selected reaction monitoring transitions of <i>m</i>/<i>z</i> 931.5 → 864.4 and <i>m/z</i> 809.5 → 756.5 were applied for sirolimus and ascomycin (the internal standard, IS), respectively. The method was selective and linear over a concentration range of 0.5–50 ng/mL. The method was validated for sensitivity, accuracy, precision, extraction recovery, matrix effect, and stability in porcine whole blood and lung tissue homogenates, and all values were within acceptable ranges. The method was applied to a pharmacokinetic study to quantitate sirolimus levels in porcine blood and its distribution in lung tissue following the application of stents in the porcine coronary arteries. It enabled the quantification of sirolimus concentration until 2 and 14 days in blood and in lung tissue, respectively. This method would be appropriate for both routine porcine pharmacokinetic and bio-distribution studies of sirolimus formulations.https://www.mdpi.com/1420-3049/26/2/425sirolimusLC-MS/MSvalidationwhole bloodlung tissuepharmacokinetic |
| spellingShingle | Thi-Thao-Linh Nguyen Van-An Duong Dang-Khoa Vo Jeongae Jo Han-Joo Maeng Development and Validation of a Bioanalytical LC-MS/MS Method for Simultaneous Determination of Sirolimus in Porcine Whole Blood and Lung Tissue and Pharmacokinetic Application with Coronary Stents Molecules sirolimus LC-MS/MS validation whole blood lung tissue pharmacokinetic |
| title | Development and Validation of a Bioanalytical LC-MS/MS Method for Simultaneous Determination of Sirolimus in Porcine Whole Blood and Lung Tissue and Pharmacokinetic Application with Coronary Stents |
| title_full | Development and Validation of a Bioanalytical LC-MS/MS Method for Simultaneous Determination of Sirolimus in Porcine Whole Blood and Lung Tissue and Pharmacokinetic Application with Coronary Stents |
| title_fullStr | Development and Validation of a Bioanalytical LC-MS/MS Method for Simultaneous Determination of Sirolimus in Porcine Whole Blood and Lung Tissue and Pharmacokinetic Application with Coronary Stents |
| title_full_unstemmed | Development and Validation of a Bioanalytical LC-MS/MS Method for Simultaneous Determination of Sirolimus in Porcine Whole Blood and Lung Tissue and Pharmacokinetic Application with Coronary Stents |
| title_short | Development and Validation of a Bioanalytical LC-MS/MS Method for Simultaneous Determination of Sirolimus in Porcine Whole Blood and Lung Tissue and Pharmacokinetic Application with Coronary Stents |
| title_sort | development and validation of a bioanalytical lc ms ms method for simultaneous determination of sirolimus in porcine whole blood and lung tissue and pharmacokinetic application with coronary stents |
| topic | sirolimus LC-MS/MS validation whole blood lung tissue pharmacokinetic |
| url | https://www.mdpi.com/1420-3049/26/2/425 |
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