المؤلفون: Justin Jarrah, Rebecca L. Harney, Hadia K. Riaz, Salvatore J. Salamone, Hongxia Zhang, Daniel J. Cline, Gregory D. Lundell, Jodi Blake Courtney, Yunying Li, Irina Baburina, Makoto Miyazaki

المصدر: Therapeutic Drug Monitoring. 35:809-815

مصطلحات موضوعية: Oncology, endocrine system, medicine.medical_specialty, Validation study, Paclitaxel, Automation, chemistry.chemical_compound, Breast cancer, Limit of Detection, Tandem Mass Spectrometry, Internal medicine, medicine, Humans, Pharmacology (medical), Prospective Studies, Prospective cohort study, Chromatography, High Pressure Liquid, Immunoassay, Pharmacology, medicine.diagnostic_test, business.industry, Reproducibility of Results, medicine.disease, Antineoplastic Agents, Phytogenic, chemistry, Immunology, Nanoparticles, Non small cell, Drug Monitoring, business, Ovarian cancer

الوصف: Paclitaxel (PTX; Taxol, Abraxane) is used in many regimens for breast cancer, non-small cell lung cancer (NSCLC), and ovarian cancer. Multiple studies have demonstrated that PTX exhibits a greater than 10-fold interpatient variability of clearance rates when patients are dosed according to body surface area (BSA). Pharmacokinetic and pharmacodynamic relationships have been elucidated from BSA-based dosing. PTX is a candidate for dose management, and studies have shown that therapeutic dose management (TDM) is feasible and may provide improved outcomes for patients undergoing treatment.A PTX immunoassay (MyPaclitaxel) has been developed, which employs a novel PTX monoclonal antibody in a nanoparticle-based turbidimetric assay in a competitive format. Precision, accuracy, and linearity were evaluated by Clinical Laboratory Standards Institute protocols at 3 laboratories on the Olympus AU400 analyzer. Method comparison was done versus a validated high-performance liquid chromatography-tandem mass spectroscopy method using samples (n = 119) collected from patients on PTX therapy.The assay requires 8 μL of plasma sample and can produce 400 determinations per hour. The response curve is based on a 6-point nonlinear curve fit and has a range of 0-320 ng/mL, extended to 3200 ng/mL with 10-fold autodilution. Three controls and 4 patient pools were used in precision studies. For all samples across 3 sites, repeatability coefficient of variation percentages ranged 0.9%-4.9%, and within-laboratory coefficient of variation percentages were 1.0%-4.2% with standard curve stability up to 24 days. Linearity was demonstrated over the linear range. Lower limits of detection and quantitation were 11 and 19 ng/mL, respectively. Method comparison results were analyzed by Deming regression, demonstrating a slope = 1.002 and intercept = -3.029 and an R = 0.996. The PTX samples ranged from 24 to 3164 ng/mL with a mean of 745 ng/mL.The analytical performance of an automated immunoassay for PTX has been validated and may serve as a useful tool for TDM of this drug.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bcf909c0b6543a6c5585d596a21d48a9
https://doi.org/10.1097/ftd.0b013e318296be01

المؤلفون: Sandy Lepp, Erick Gamelin, Merrill J. Egorin, Gérard Milano, Salvatore J. Salamone, Rebecca L. Harney, Gregory D. Lundell, M. Boisdron-Celle, Catherine A. Hammett-Stabler, Yunying Li, Jodi Blake Courtney, Jan H. Beumer, Gwen McMillin, William Clarke

المصدر: Therapeutic Drug Monitoring. 31:688-694

مصطلحات موضوعية: Pharmacology, Drug, Oncology, Chemotherapy, medicine.medical_specialty, biology, medicine.diagnostic_test, medicine.drug_class, business.industry, media_common.quotation_subject, medicine.medical_treatment, Thymidylate synthase, Antimetabolite, Pharmacokinetics, Fluorouracil, Immunoassay, Internal medicine, Toxicity, biology.protein, medicine, Pharmacology (medical), business, media_common, medicine.drug

الوصف: Background:5-Fluorouracil (5-FU) is the most widely used chemotherapy drug, primarily against gastrointestinal, head and neck, and breast cancers. 5-FU has large pharmacokinetic variability resulting in unexpected toxicity or ineffective treatment. Therapeutic drug management of 5-FU minimizes toxic

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::f7db2ce134e020890d5e44ebbce68c90
https://doi.org/10.1097/ftd.0b013e3181b9b8c0

المؤلفون: Gregory D. Lundell, Yunying Li, Rebecca L. Harney, Rita Gonzalez-Espinoza, Gwendolyn A. McMillin, JoEtta M. Juenke, Geeta Agarwal, Anu Mathew, Salvatore J. Salamone, Martin Fleisher, Jodi Blake Courtney

المصدر: Therapeutic Drug Monitoring. 31:489-494

مصطلحات موضوعية: Male, Pharmacology, Alkylating Agents, Chromatography, Dose-Response Relationship, Drug, medicine.diagnostic_test, Chemistry, Coefficient of variation, Enzyme-Linked Immunosorbent Assay, Reference Standards, Standard curve, Microtiter plate, Immunoassay, Blood plasma, medicine, Humans, Pharmacology (medical), Sample preparation, Antineoplastic Agents, Alkylating, Busulfan, Quantitative analysis (chemistry), medicine.drug

الوصف: High-dose busulfan is an important component of many bone marrow transplantation-preparative regimens. High busulfan plasma levels have been shown to increase the chance of venoocclusive disease and low levels are associated with recurrence of disease or graft rejection. Currently, busulfan levels are monitored by physical methods that are expensive and time consuming, resulting in relatively low overall use of busulfan testing for dose adjustment. Novel highly selective antibodies for busulfan have been generated and a microtiter plate immunoassay capable of quantifying busulfan levels in plasma has been developed. The assay was configured using a busulfan-horseradish peroxidase (HRP) conjugate as the reporter group and busulfan monoclonal antibodies. The assay requires 30 microL of plasma with no sample preparation. The immunoassay has a standard curve based on busulfan with a range of 75-2000 ng/mL. The time to first result is 30 minutes with up to 40 patient samples in duplicate; multiple plates can be run at once. The coefficient of variation (CV) on signal is

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fab55fec85601aa2dafcaa3b02e4f0bb
https://doi.org/10.1097/ftd.0b013e3181a8c99c

المؤلفون: Yunying Li, Hongxia Zhang, Justin Jarrah, Daniel J. Cline, Gregory D. Lundell, Rebecca L. Harney, Salvatore J. Salamone, Irina Baburina, Makoto Miyazaki, Hadia K. Riaz, Jodi Blake Courtney

المصدر: Therapeutic drug monitoring. 35(6)

مصطلحات موضوعية: Drug, Oncology, medicine.medical_specialty, media_common.quotation_subject, medicine.medical_treatment, Analytical chemistry, Antineoplastic Agents, Docetaxel, Automation, Therapeutic index, Breast cancer, Prostate, Limit of Detection, Nephelometry and Turbidimetry, Tandem Mass Spectrometry, Internal medicine, medicine, Humans, Pharmacology (medical), Prospective Studies, Prospective cohort study, media_common, Pharmacology, Immunoassay, Chemotherapy, medicine.diagnostic_test, business.industry, Reproducibility of Results, medicine.disease, medicine.anatomical_structure, Sample Size, Nanoparticles, Taxoids, Drug Monitoring, business, medicine.drug, Chromatography, Liquid

الوصف: Docetaxel (Taxotere) (DTX) is a widely used chemotherapy agent used in many regimens for the treatment of solid tumors, for example breast cancer, non-small cell lung cancer, gastric, prostate, and head and neck cancers. This drug meets the criteria for therapeutic dose management, in that it is associated with high pharmacokinetic variability and dose-limiting toxicity; it has a narrow therapeutic window, and there is a significant pharmacokinetic-pharmacodynamic relationship. Measures of exposure and area under the time-concentration curve have been associated with both toxicity and outcomes, making therapeutic dose management for this drug an unmet clinical need. The current methodologies for measuring DTX are based on physical methods, making the analysis less available and costly. An automated immunoassay has been developed to provide greater access to DTX dose management.A DTX immunoassay (MyDocetaxel) has been developed using a generic nanoparticle turbidimetric method that can be used on a wide variety of automated clinical chemistry analyzers including the Beckman Coulter AU400 and AU640 instruments, which were used in this study. The assay is based on a competitive assay format using a selective DTX monoclonal antibody. Clinical Laboratory Standards Institute protocols for establishing manufacturer's claims were used to verify performance. Testing at 3 clinical laboratories was undertaken using the same protocols for laboratory validation of precision, accuracy, and linearity. Method comparison (n = 89) was done using samples collected from patients on DTX therapy. The comparative method was LC-MS/MS validated according to Food and Drug Administration guidance on bioanalytical methods. Institutional review board approval was obtained for prospective collection of samples from patients on DTX therapy.The assay on the AU400 uses 2 μL of sample, provides the first result in 9.0 minutes and can generate 400 determinations per hour. Internal studies established a lower limit of detection ≤25 ng/mL and a lower limit of quantitation ≤30 ng/mL. Additional studies demonstrated no interference from coadministered drugs, major metabolites, or related compounds. Linearity from 50 to 1000 ng/mL was validated. Method comparisons between laboratories and to the physical method gave slopes: 1 ± 0.5, intercepts:2.0 ng/mL, R0.99, with the range of DTX concentrations measured by the assay 31-9754 ng/mL, with a mean of 689 ng/mL. In all 3 laboratories, the coefficient of variation percentage for repeatability ranged from 0.8% to 6.2% and the within-laboratory precision ranged from 1.4% to 10.1%.This immunoassay is suitable for quantifying DTX in plasma with advantages of small sample size, no sample pretreatment, and the ability to be applied to a wide range of clinical analyzers. With the validation of this method, the application of DTX testing in clinical practice may gain wider acceptance for individualizing patient DTX dosing.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::38d4f4375dc7a8cac8aa942f56866c2e
https://pubmed.ncbi.nlm.nih.gov/24263639

المؤلفون: Jan H, Beumer, M, Boisdron-Celle, William, Clarke, Jodi B, Courtney, Merrill J, Egorin, Erick, Gamelin, Rebecca L, Harney, Catherine, Hammett-Stabler, Sandy, Lepp, Yunying, Li, Gregory D, Lundell, Gwen, McMillin, Gerard, Milano, Salvatore J, Salamone

المصدر: Therapeutic drug monitoring. 31(6)

مصطلحات موضوعية: Immunoassay, Time Factors, Limit of Detection, Nephelometry and Turbidimetry, Calibration, Antibodies, Monoclonal, Humans, Nanoparticles, Reproducibility of Results, Fluorouracil, Drug Monitoring

الوصف: 5-Fluorouracil (5-FU) is the most widely used chemotherapy drug, primarily against gastrointestinal, head and neck, and breast cancers. 5-FU has large pharmacokinetic variability resulting in unexpected toxicity or ineffective treatment. Therapeutic drug management of 5-FU minimizes toxicity and improves outcome. A nanoparticle-based immunoassay was developed to provide oncologists with a rapid, cost-effective tool for determining 5-FU plasma concentrations.Monoclonal antibodies, bound to nanoparticles, were used to develop an immunoassay for the Olympus AU400. Assay precision, linearity, calibration stability, and limit of detection were run at multiple centers; interference, cross-reactivity, lower limit of quantitation and recovery at 1 center. Clinical samples collected from 4 cancer centers were analyzed for 5-FU concentrations by liquid chromatography-tandem mass spectrometry and compared with the immunoassay results.With calibrators from 0 to 1800 ng/mL 5-FU and autodilution, concentrations up to 9000 ng/mL could be determined. Time to first result was 10 minutes, and 400 samples per hour could be quantitated from a standard curve stored for30 days. Imprecision across all laboratories was5%, and the assay was linear upon dilution over the entire range. Cross-reactivities for dihydro-5-FU, uracil, capecitabine, and tegafur were1%, 9.9%, 0.05%, and 0.23%, respectively. The limit of detection was 52 ng/mL with a lower limit of quantitation of 86 ng/mL. Assay results of clinical samples (93-1774 ng/mL) correlated with liquid chromatography-tandem mass spectrometry results: (R = 0.9860, slope 1.035, intercept 10.87 ng/mL).This novel immunoassay is suitable for quantitating 5-FU plasma concentrations with advantages of speed, small sample size, minimal sample pretreatment, and application on automated instrumentation. These advantages enable efficient therapeutic drug management of 5-FU in clinical practice.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=pmid________::e6fd706609b1375cf360852286e450a1
https://pubmed.ncbi.nlm.nih.gov/19935361