Kamma Harsha Sri , Panchumarthy Ravisankar , Sathish Kumar Konidala , P. Srinivasa Babu
{"title":"将新开发和验证的 LC-MS/MS 方法同时用于大鼠血浆中阿达拉昔布和彭博利珠单抗的药代动力学研究","authors":"Kamma Harsha Sri , Panchumarthy Ravisankar , Sathish Kumar Konidala , P. Srinivasa Babu","doi":"10.1016/j.jchromb.2024.124171","DOIUrl":null,"url":null,"abstract":"<div><p>Non-small cell lung cancer (NSCLC) is a significant subtype of lung cancer, and poses a dangerous global threat. One of the current approaches of NSCLC treatment is a combination therapy of adagrasib and pembrolizumab. Accurate monitoring of these drug concentrations in biological fluids is critical for treatment efficacy. Since no method was reported for simultaneous estimation of these drugs, this study focuses on the development of a validated LC-MS/MS bioanalytical method for simultaneous quantification of Adagrasib and Pembrolizumab in rat plasma. The analytes were extracted from the biological matrix through liquid–liquid extraction techniques using acetonitrile as extraction solvent. The analytes were separated on a Waters X-bridge phenyl C<sub>18</sub> column, with a mixture of acetonitrile: 0.1 % TFA in water (50: 50 v/v) as mobile phase at an isocratic flow rate of 1.0 mL/min with a runtime of about 5 min. Adagrasib (<em>m</em>/<em>z</em> 605.12 <span><math><mrow><mo>→</mo></mrow></math></span> 201.62), Pembrolizumab (<em>m</em>/<em>z</em> 146.32 <span><math><mrow><mo>→</mo></mrow></math></span> 85.15), and Sotorasib (<em>m</em>/<em>z</em> 561.59 <span><math><mrow><mo>→</mo></mrow></math></span> 218.92) were determined by recording the mass spectra through multiple reaction monitoring in positive mode. The method was validated according to USFDA guidelines. The results demonstrate satisfactory linearity with an r<sup>2</sup> value of 0.9998 in the ranges of 40–800 and 10–200 ng/mL, accuracy with mean percentage recovery of 95.22–98.59 % and 96.98–98.57 %, precision indicated with %RSD ranged between 0.39–1.91 % and 0.85–9.03 % for Adagrasib and Pembrolizumab respectively, and other key parameters. The developed method can determine the pharmacokinetic parameters to indicate the efficacy and safety of the drugs, and also can quantify selected drugs simultaneously in biological samples.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Application of newly developed and validated LC-MS/MS method for pharmacokinetic study of adagrasib and pembrolizumab simultaneously in rat plasma\",\"authors\":\"Kamma Harsha Sri , Panchumarthy Ravisankar , Sathish Kumar Konidala , P. Srinivasa Babu\",\"doi\":\"10.1016/j.jchromb.2024.124171\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Non-small cell lung cancer (NSCLC) is a significant subtype of lung cancer, and poses a dangerous global threat. One of the current approaches of NSCLC treatment is a combination therapy of adagrasib and pembrolizumab. Accurate monitoring of these drug concentrations in biological fluids is critical for treatment efficacy. Since no method was reported for simultaneous estimation of these drugs, this study focuses on the development of a validated LC-MS/MS bioanalytical method for simultaneous quantification of Adagrasib and Pembrolizumab in rat plasma. The analytes were extracted from the biological matrix through liquid–liquid extraction techniques using acetonitrile as extraction solvent. The analytes were separated on a Waters X-bridge phenyl C<sub>18</sub> column, with a mixture of acetonitrile: 0.1 % TFA in water (50: 50 v/v) as mobile phase at an isocratic flow rate of 1.0 mL/min with a runtime of about 5 min. Adagrasib (<em>m</em>/<em>z</em> 605.12 <span><math><mrow><mo>→</mo></mrow></math></span> 201.62), Pembrolizumab (<em>m</em>/<em>z</em> 146.32 <span><math><mrow><mo>→</mo></mrow></math></span> 85.15), and Sotorasib (<em>m</em>/<em>z</em> 561.59 <span><math><mrow><mo>→</mo></mrow></math></span> 218.92) were determined by recording the mass spectra through multiple reaction monitoring in positive mode. The method was validated according to USFDA guidelines. The results demonstrate satisfactory linearity with an r<sup>2</sup> value of 0.9998 in the ranges of 40–800 and 10–200 ng/mL, accuracy with mean percentage recovery of 95.22–98.59 % and 96.98–98.57 %, precision indicated with %RSD ranged between 0.39–1.91 % and 0.85–9.03 % for Adagrasib and Pembrolizumab respectively, and other key parameters. The developed method can determine the pharmacokinetic parameters to indicate the efficacy and safety of the drugs, and also can quantify selected drugs simultaneously in biological samples.</p></div>\",\"PeriodicalId\":348,\"journal\":{\"name\":\"Journal of Chromatography B\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-05-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Chromatography B\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1570023224001806\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chromatography B","FirstCategoryId":"1","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1570023224001806","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Application of newly developed and validated LC-MS/MS method for pharmacokinetic study of adagrasib and pembrolizumab simultaneously in rat plasma
Non-small cell lung cancer (NSCLC) is a significant subtype of lung cancer, and poses a dangerous global threat. One of the current approaches of NSCLC treatment is a combination therapy of adagrasib and pembrolizumab. Accurate monitoring of these drug concentrations in biological fluids is critical for treatment efficacy. Since no method was reported for simultaneous estimation of these drugs, this study focuses on the development of a validated LC-MS/MS bioanalytical method for simultaneous quantification of Adagrasib and Pembrolizumab in rat plasma. The analytes were extracted from the biological matrix through liquid–liquid extraction techniques using acetonitrile as extraction solvent. The analytes were separated on a Waters X-bridge phenyl C18 column, with a mixture of acetonitrile: 0.1 % TFA in water (50: 50 v/v) as mobile phase at an isocratic flow rate of 1.0 mL/min with a runtime of about 5 min. Adagrasib (m/z 605.12 201.62), Pembrolizumab (m/z 146.32 85.15), and Sotorasib (m/z 561.59 218.92) were determined by recording the mass spectra through multiple reaction monitoring in positive mode. The method was validated according to USFDA guidelines. The results demonstrate satisfactory linearity with an r2 value of 0.9998 in the ranges of 40–800 and 10–200 ng/mL, accuracy with mean percentage recovery of 95.22–98.59 % and 96.98–98.57 %, precision indicated with %RSD ranged between 0.39–1.91 % and 0.85–9.03 % for Adagrasib and Pembrolizumab respectively, and other key parameters. The developed method can determine the pharmacokinetic parameters to indicate the efficacy and safety of the drugs, and also can quantify selected drugs simultaneously in biological samples.
期刊介绍:
The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis.
Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches.
Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.