Therapeutic Drug Monitoring最新文献

{"title":"Broad-Spectrum Drug Screening Positivity Rates in Pediatrics and Adults: The Reference Laboratory Perspective.","authors":"Ryan C Shean, Kamisha L Johnson-Davis","doi":"10.1097/FTD.0000000000001400","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001400","url":null,"abstract":"<p><strong>Background: </strong>Broad-spectrum drug testing is useful in various practical settings, especially when patients present with unknown exposures. Although national poison control data inform trends in toxicity and poison control calls, a need exists for clinical drug detection data across different patient populations.</p><p><strong>Methods: </strong>To address this need, this retrospective study analyzed drug positivity rates from plasma and urine samples tested on a 127-analyte broad-spectrum drug panel. Samples were stratified by sex and age groups (pediatric <18 years, adult ≥18 years). Positivity rates for drug classes and copositivity patterns were compared using χ2 testing with Bonferroni correction.</p><p><strong>Results: </strong>In total, 7750 samples (3140 plasma and 4610 urine) were analyzed. Positivity for at least one of the tested analytes was high (86% in plasma and 82% in urine). In urine, significant differences in positivity rates between male and female patients were observed for anticonvulsants, antidepressants, antihistamines, benzodiazepines, muscle relaxants, and nicotine. All substances were more prevalent in female patients, except nicotine. Copositivity was more common in female patients, who were more likely than male patients to test positive for 2 or more drug classes. Pediatrics were more likely than adults to test positive for sedatives but less likely for most other drug classes. Overall, patterns of drug class detection differed significantly by age and sex.</p><p><strong>Conclusions: </strong>This retrospective study reports real-world positivity patterns in a broad-spectrum drug panel, including significant sex- and age-based differences. The higher rates of copositivity in female patients and the higher prevalence of sedatives in pediatric patients are clinically relevant for interpreting drug screen results and managing acute toxidromes. These findings may be useful to both acute care decision making and public health policy interventions, particularly in the pediatric setting.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Evaluation of Multimodel Informed Precision Dosing Tool for Optimizing Vancomycin Therapy in Pediatric Patients.","authors":"Yawen Yuan, Li Xu, Yueling Xi, Zhonghui Huang, Jing Cao, Zhiling Li, Joseph F Standing","doi":"10.1097/FTD.0000000000001392","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001392","url":null,"abstract":"<p><strong>Background: </strong>The narrow therapeutic window and high pharmacokinetic (PK) variability of vancomycin may lead to trough concentrations outside the usual therapeutic range, requiring dose adjustments. In this study, we aimed to identify suitable pediatric vancomycin models, evaluate their predictive performance, and develop an RShiny-based multimodel informed precision-dosing (multi-MIPD) tool.</p><p><strong>Methods: </strong>A systematic literature search was undertaken to identify pediatric vancomycin PK models, which were graded according to published quality-assessment criteria. Retrospective vancomycin therapeutic drug monitoring data were used to evaluate the performance of high-quality models. Consensus models (mean, median, and weighted) were constructed. In addition, a MIPD tool was developed using the free R package Shiny and validated for both initial dosing and dose adjustment. This tool was evaluated using a prospective dataset.</p><p><strong>Results: </strong>Nine models demonstrated excellent predictive performance in the retrospective data set (311 concentrations from 192 patients), with root-mean-square error values ranging from 1.00 to 1.97 mg/L and median individual prediction errors from -0.46 to 0.42 mg/L. The multi-MIPD tool incorporating 9 models is presented in the Supplemental Digital Content 1 (see Appendix, http://links.lww.com/TDM/A894). The optimal model achieved a median individual prediction errors of 0.02 mg/L, and an root-mean-square error of 0.12 mg/L in the prospective data set (42 concentrations from 35 patients). The mean consensus model significantly improved target area under the curve attainment compared with empirical dosing, with 68.73% versus 36.53% for initial dosing and 55.56% versus 22.22% after dose adjustments.</p><p><strong>Conclusions: </strong>The multi-MIPD tool provided accurate concentration predictions and, compared with empirical dosing, significantly improved vancomycin target attainment, offering a more effective and individualized dosing strategy for pediatric patients.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylene Blue-Induced False-Positive Amphetamine Results in Urine Drug Screening: Two Case Reports.","authors":"Emiel Leegwater, Nynke G L Jager","doi":"10.1097/FTD.0000000000001396","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001396","url":null,"abstract":"","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Drug Monitoring and Point-of-Care Technologies: Opportunities and Current Challenges.","authors":"Sandro Carrara, Nicolas Widmer, Francesca Rodino, Lin Du, Myriam Briki, Laurent A Decosterd, Catia Marzolini, Thierry Buclin, Yann Thoma, Monia Guidi","doi":"10.1097/FTD.0000000000001384","DOIUrl":"10.1097/FTD.0000000000001384","url":null,"abstract":"<p><strong>Background: </strong>This review re-evaluates therapeutic drug monitoring (TDM) by comparing the current analytical and subsequent clinical interpretation capabilities of hospital or community medical laboratories with the emerging potential of point-of-care (POC) devices, which could become increasingly utilized in hospital wards, day-hospital units, and outpatient clinic settings.</p><p><strong>Methods: </strong>A narrative review was conducted to identify publications that best illustrate the current trends in the development of POC TDM.</p><p><strong>Results: </strong>The latest scientific and technical literature indicates that POC devices for determining drug concentrations in clinical samples are approaching the market. Several technologies are now available to develop portable sensors capable of rapidly returning concentration measurements. Interfacing these methods with artificial intelligence-based pattern recognition may enhance the identification and quantification of drugs. However, once the drug concentration is accurately measured using a portable device, dosage adjustments require consideration of the drug's pharmacokinetics and the patient's characteristics. This is accounted for in the mathematical approaches underlying model-informed precision dosing, which consider inter- and intra-individual variability and provide recommendations for treatment adjustments. These complexities necessitate the use of digital technologies, including graphical interfaces, machine learning approaches, and secure connectivity, to enhance the application of TDM in clinical practice.</p><p><strong>Conclusions: </strong>Promising emerging technologies have considerable potential to expand TDM to cover a wide range of drugs, making precision medicine accessible to many patients.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cefepime Pharmacokinetics in Patients Receiving Extracorporeal Membrane Oxygenation.","authors":"Nicole F Maranchick, Andrew Jaudon, Siya Aparanji, Emma Carruthers, Nathalia Rodriguez, Cristina Phillips, David Knott, Abbas Shahmohammadi, Charles A Peloquin, Mohammad H Alshaer","doi":"10.1097/FTD.0000000000001394","DOIUrl":"10.1097/FTD.0000000000001394","url":null,"abstract":"<p><strong>Background: </strong>Data on the effect of extracorporeal membrane oxygenation (ECMO) on cefepime concentration and protein binding are limited. This study aimed to describe the pharmacokinetics of cefepime in patients receiving ECMO, with or without renal replacement therapy.</p><p><strong>Methods: </strong>Participants receiving ECMO were prospectively enrolled in the thoracic and lung transplant intensive care unit at the University of Florida Health-Shands Hospital in Gainesville, FL. Serum samples for drug quantification were collected at 1, 2, 4, 6, and 8 hours after the completion of cefepime infusion, pre- and post-ECMO oxygenator. The total and free drug concentrations in the ultrafiltrate were measured using liquid chromatography-tandem mass spectrometry at the University of Florida Infectious Disease Pharmacokinetics Laboratory.</p><p><strong>Results: </strong>Six patients who underwent venovenous ECMO were enrolled in the study. The median [interquartile range (IQR)] age and weight were 56.5 years (48-61.8) and 80.6 kg (75.4-90.6), respectively, and 67% were female. All patients received 2 g of cefepime infused over 30 minutes, with dosing intervals per renal function. The median (IQR) time between ECMO initiation and pharmacokinetic sampling was 3.5 days (2.5-24.7). None of the patients underwent renal replacement therapy during sampling. Minimal differences in cefepime concentrations pre- and postoxygenator were observed (<20% difference for all paired samples; median 3.5%). The median (IQR) protein-binding rates for cefepime both pre- [6.2% (2.6-10.8)] and post- [8.7% (2.5-13.4)] oxygenator were lower than previously published estimates of 20%.</p><p><strong>Conclusions: </strong>No differences in pre- or post-ECMO oxygenator cefepime concentrations were observed. The median protein-binding values were less than previously published values.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Quantification of Four Endocannabinoids and Endocannabinoid-Like Substances in Plasma: Application in an HIV-Hepatitis C Virus Coinfected Population.","authors":"Alexandr Gish, Eqbal Radwan, Camille Richeval, Camelia Protopopescu, Jean-François Wiart, Florian Hakim, Delphine Allorge, Patrizia Carrieri, Tangui Barré, Jean-Michel Gaulier","doi":"10.1097/FTD.0000000000001397","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001397","url":null,"abstract":"<p><strong>Background: </strong>The endocannabinoid system regulates immune function, inflammation, and metabolism and has gained increasing attention in clinical research. However, the instability, low abundance, and physicochemical complexity of endocannabinoids (ECs) and EC-like substances (EC-like) make their quantification in plasma analytically challenging.</p><p><strong>Objective and methods: </strong>The authors developed and validated a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of N-arachidonoylethanolamide (AEA), 2-arachidonoylglycerol, and its isomer 1-arachidonoylglycerol (2-AG/1-AG), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA) in human plasma.</p><p><strong>Results: </strong>Extraction was performed using liquid-liquid extraction combined with liquid chromatography-tandem mass spectrometry. The method achieved lower limits of quantification of 0.1 mcg/L for AEA, 0.2 mcg/L for 2-AG/1-AG, and 0.5 mcg/L for OEA and PEA, with calibration curves showing high linearity (R2 ≥ 0.995). Intra-assay and interassay accuracy and precision were both within 15%. Additional validation parameters, including selectivity, recovery, carryover, matrix suitability, and dilution integrity, fulfilled regulatory criteria. Preanalytical handling significantly influenced concentrations: Delayed centrifugation and postthaw storage increased AEA, OEA, and PEA levels. The validated method was applied to plasma samples from patients coinfected with HIV and hepatitis C virus, enabling reproducible quantification of ECs and EC-like substances in a clinically relevant cohort.</p><p><strong>Conclusions: </strong>The study demonstrates that biological and technical factors markedly affect plasma EC and EC-like concentrations. Standardized preanalytical processing is therefore essential for accurate measurement, and the proposed method provides a robust tool for clinical and pharmacological research.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a UHPLC-MS/MS Method for the Determination of Omadacycline in Human Plasma.","authors":"Chuang Chen, Yao-Jie Chen, Jing Fu, Yu-Zhen Wang, Sun-Ting Qin, Meng-Yu Kong, Guan-Yang Lin, Xiu-Hua Zhang, Xu-Ben Yu","doi":"10.1097/FTD.0000000000001308","DOIUrl":"10.1097/FTD.0000000000001308","url":null,"abstract":"<p><strong>Abstract: </strong>Omadacycline is a novel aminomethylcycline antibiotic that retains its antibacterial activity against strain-specific efflux pumps and ribosomal protective protein mechanisms of tetracycline resistance. To determine the concentration of omadacycline in human plasma, an ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed to provide a basis for therapeutic monitoring of omadacycline in clinical settings. The experimental approach involves using an ACQUITY UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm), with a mobile phase of 0.1% aqueous formic acid:acetonitrile (90:10, vol/vol), a flow rate of 0.3 mL·min -1 , a column temperature of 40°C, and an injection volume of 0.1 μL. Protein precipitation was employed as pretreatment, using acetonitrile as the precipitant. Minocycline was used as an internal standard. Omadacycline and internal standard were monitored in positive ion mode with the following mass transition pairs: mass/charge (m/z) = 557.1→ 470.1 for omadacycline, and m/z = 458.3→ 440.9 for IS, respectively. The established method showed a good linearity in the range of 0.01-10 mcg/mL of omadacycline (Y = 0.4603X + 0.0452, r 2 = 0.999), with the lower limit of quantification of 0.01 mcg/mL. Method validation included accuracy, precision, matrix effect, recovery, carryover, dilution integrity, and stability, all of which met the requirements of the US Food and Drug Administration for the validation of bioanalytical methods. This method has been successfully applied to therapeutic drug monitoring in patients.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"587-593"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective Validation of a Nomogram for Determining the Optimal Dose of Lamotrigine for Augmentation Therapy in Patients With Treatment-Resistant Depression.","authors":"Takeshi Suzuki, Goyo Nagai, Kazuo Mihara, Yoko Tomori, Shoko Kagawa, Akifumi Nakamura, Kenji Nemoto, Tsuyoshi Kondo","doi":"10.1097/FTD.0000000000001316","DOIUrl":"10.1097/FTD.0000000000001316","url":null,"abstract":"<p><strong>Background: </strong>Previous research has shown that a plasma lamotrigine concentration of 12.7 µmol/L may be a threshold for a good therapeutic response to lamotrigine augmentation therapy in Japanese patients with treatment-resistant depression. The optimal dose of lamotrigine can be predicted using a previously established nomogram based on the plasma lamotrigine concentration at week 2. The aim of the present study was to prospectively evaluate the validity of this nomogram.</p><p><strong>Methods: </strong>Participants included 59 patients with depression who showed insufficient therapeutic responses to psychotropics, including antidepressants, antipsychotics, and mood stabilizers. The patients were diagnosed with major depressive disorder (n = 26), bipolar II disorder (n = 25), or bipolar I disorder (n = 8). Lamotrigine was administered to all the patients. The initial dose of lamotrigine was 25 mg/d for 32 patients not taking valproate and 25 mg/d every other day for 27 patients taking valproate. Blood samples were collected at week 2 and at least 2 weeks after the final daily dose, which was estimated by a nomogram based on the plasma lamotrigine concentration at week 2. The plasma concentrations of lamotrigine were measured by liquid chromatography-mass spectrometry.</p><p><strong>Results: </strong>In 30 of the 32 patients (93.8%) who were not taking valproate and 23 of the 27 patients (85.2%) who were taking valproate, a plasma lamotrigine concentration of 12.7 mcg/mL or higher was achieved at the final daily administration of lamotrigine.</p><p><strong>Conclusions: </strong>The results of the present study suggest that the previously established nomogram is valid for determining the optimal dose of lamotrigine for Japanese patients with treatment-resistant depression in clinical settings.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"648-652"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Application of Volumetric Absorptive Microsampling for Therapeutic Drug Monitoring of Oral Targeted Anticancer Drugs.","authors":"Marinda Meertens, Nikki Kerssemakers, Niels de Vries, Hilde Rosing, Neeltje Steeghs, Jos H Beijnen, Alwin D R Huitema","doi":"10.1097/FTD.0000000000001315","DOIUrl":"10.1097/FTD.0000000000001315","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic drug monitoring optimizes oral anticancer drug treatment by measuring plasma levels. Volumetric absorptive microsampling (VAMS) allows home sampling with a minimal blood sample. However, methods for converting whole blood into plasma are required to interpret these results. This study aimed to establish conversion methods for abiraterone, alectinib, cabozantinib, imatinib, olaparib, sunitinib, and their metabolites, while assessing the differences between venous and capillary blood. The feasibility of home sampling was also evaluated.</p><p><strong>Methods: </strong>Plasma and VAMS samples, both from venipuncture-collected whole blood tubes and from a finger prick, were collected from each patient. The VAMS samples were deemed comparable if their concentrations were within ±20% of each other for ≥2/3rd of the patients. The Passing-Bablok regression and conversion factor methods were tested for the plasma and VAMS finger prick samples. The estimated plasma concentrations using both methods were required to be within ±20% of the measured plasma concentrations for ≥2/3rd of the pairs.</p><p><strong>Results: </strong>Overall, 153 patients were enrolled in this study. Conversion methods were applied to the VAMS samples, and the acceptance criteria were met for alectinib-M4, cabozantinib, imatinib, N-desmethyl imatinib, olaparib, sunitinib, and N-desethyl sunitinib but not for abiraterone, D4A, or alectinib. The capillary and venous VAMS concentrations were similar, except for that of D4A. Patients were positive toward home sampling.</p><p><strong>Conclusions: </strong>The established VAMS conversion methods for 7 out of 10 oral targeted anticancer drugs or metabolites met the acceptance criteria. Future studies need to validate the conversion methods with an independent cohort and integrate home sampling via VAMS to provide patients with an alternative to venipuncture at the outpatient clinic.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"625-634"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Offline SPE-LC-MS/MS Method for Simultaneous Quantification of Tacrolimus, Cyclosporine A, Kynurenine, Tryptophan, and Creatinine Using Volumetric Absorptive Microsampling Device Mitra.","authors":"Kajetan Nierychlewski, Katharina Habler, Stephan Kemmner, Tobias Seibt, Michael Fischereder, Markus Schwarz","doi":"10.1097/FTD.0000000000001341","DOIUrl":"10.1097/FTD.0000000000001341","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic drug monitoring of immunosuppressants is critical in balancing insufficient immunosuppression due to underdosing, and severe adverse effects due to overdosage. For a more comprehensive therapeutic drug monitoring and follow-up of transplant patients, the aim was to develop a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of tacrolimus, cyclosporine A, tryptophan, kynurenine, and creatinine using a volumetric absorptive microsampling device.</p><p><strong>Methods: </strong>Venous and capillary blood samples were simultaneously collected using a volumetric absorptive microsampling device called Mitra. The method involved protein precipitation followed by offline solid-phase extraction using a positive pressure manifold. Chromatographic separation was achieved by a formic acid-ammonium formate-methanol gradient on a Synergi Polar reversed-phase column. Multiple reaction monitoring in the positive ion mode and stable isotope-labeled internal standards were used for quantification. Validation was performed according to the European Medicines Agency and US Food and Drug Administration (FDA) guidelines.</p><p><strong>Results: </strong>Validation was successful, meeting European Medicines Agency and FDA guidelines. Investigation of selectivity, accuracy, and precision met the required criteria of a deviation <15%. Internal standards successfully compensated potential matrix effects. A comparison of 26 anonymized samples from transplant patients on Mitra with venous blood controls demonstrated the method's suitability.</p><p><strong>Conclusions: </strong>For the first time, we herein describe a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of tacrolimus, cyclosporine A, tryptophan, kynurenine, and creatinine on Mitra. Self-collection of samples may facilitate therapeutic monitoring. Simultaneous determination of creatinine may help monitor kidney function, while tryptophan and kynurenine may serve as a biomarker for early detection of transplant rejection.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"669-675"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}