OBJECTIVE: Chemotherapy-induced peripheral neuropathy (CIPN) is a major toxicity limiting the use of nab-paclitaxel (Nab-P) in treating patients with pancreatic cancer. The aim of this study was to identify the factors affecting CIPN using patient-reported outcome measures and the minimally invasive volumetric absorptive microsampling (VAMS) technique.
METHODS: The maximum concentrations of paclitaxel (Cmax) were measured from 81 VAMS samples collected from 44 participants with pancreatic cancer. The association between CIPN development and demographic, clinical and pharmacokinetic factors was determined using univariable and multivariable logistic regression. The association between CIPN severity and the factors was evaluated using Spearman\'s rank correlation. The impact of Cmax and the number of treatment cycles on the severity was assessed using multivariable linear regression.
RESULTS: The development of CIPN was significantly associated with cumulative dose (odds ratio 1.005, 95% confidence interval [CI] 1.003-1.007), treatment cycles (3.47, 2.25-5.85), alkaline phosphate (0.992, 0.985-0.998) and age (1.092, 1.020-1.179), with an area under the receiver operating characteristic curve of 0.89 (95% CI 0.83-0.95). The severity of CIPN significantly worsened with increasing cumulative dose (coefficient 0.58, 95% CI 0.44-0.69), treatment cycles (0.57, 0.44-0.68) and age (0.18, 0.00-0.35). The severity of CIPN was predictable from treatment cycles (P = .0002) and Cmax (P = .01).
CONCLUSIONS: The higher the cumulative dose of Nab-P, treatment cycles and age, the more frequently and severely do the patients experience CIPN. In predicting the severity of CIPN using Cmax, minimally invasive VAMS is a feasible alternative to venous blood sampling.

UNASSIGNED: This study aims to develop and validate bioanalytical method for quantifying warfarin in VAMS samples using liquid chromatography tandem mass spectrometry (LC-MS/MS), directly implementing the method to patients receiving warfarin therapy.
UNASSIGNED: The UPLC-MS/MS method was developed and optimized, with quercetin as the internal standard. Sample preparation was carried out using protein precipitation with methanol-acetonitrile (1:3 v/v).
UNASSIGNED: Chromatographic separation was achieved using Acquity® UPLC BEH C18 column with 0.1 % formic acid-acetonitrile-methanol (30:69:1 v/v) as mobile phase, in isocratic elution. Multiple Reaction Monitoring (MRM) detection was done using m/z values of 307.10 → 161.06 for warfarin and 301.03 → 150.98 for quercetin as internal standard, using Electrospray Ionization (ESI) negative ion source. The clinical application of the bioanalytical method was carried out on 25 patients receiving warfarin therapy at Universitas Indonesia Hospital and warfarin levels were well within the calibration range from 6.05 to 431.39 ng/mL.
UNASSIGNED: A novel method has been developed to analyze warfarin in VAMS samples. This method has been fully validated according to guideline from FDA 2022 and is linear in the range of 5-500 ng/mL and the value of r ≥ 0.9977, and successfully applied for the analysis of warfarin in VAMS samples of clinical patients.

OBJECTIVE: Dried blood volumetric absorptive microsamples (VAMS) may facilitate home-based sampling to enhance therapeutic drug monitoring after transplantation. This study aimed to clinically validate a liquid chromatography-tandem mass spectrometry assay using 2 VAMS devices with different sampling locations (Tasso-M20 for the upper arm and Mitra for the finger). Patient preferences were also evaluated.
METHODS: Clinical validation was performed for tacrolimus and mycophenolic acid by comparison of paired VAMS and venipuncture samples using Passing-Bablok regression and Bland-Altman analysis. Conversion of mycophenolic acid VAMS to serum concentrations was evaluated using haematocrit-dependent formulas and fixed correction factors defined a priori. Patients\' perspectives, including useability, acceptability and feasibility, were also investigated using established questionnaires.
RESULTS: Paired samples (n = 50) were collected from 25 kidney transplant recipients. Differences for tacrolimus whole-blood concentration were within ±20% for 86 and 88% of samples from the upper arm and fingerstick, respectively. Using correction factors of 1.3 for the upper-arm and 1.47 for finger-prick samples, 84 and 76% of the paired samples, respectively, were within ±20% for mycophenolic acid serum concentration. Patient experience surveys demonstrated limited pain and acceptable useability of the upper-arm device.
CONCLUSIONS: Tacrolimus and mycophenolic acid can be measured using 2 common VAMS devices with similar analytical performance. Patients are supportive of home-based monitoring with a preference for the Tasso-M20 device.

OBJECTIVE: Ciclosporin (CSA) is an immunosuppressive agent that requires therapeutic drug monitoring (TDM). High partitioning in erythrocytes indicates that whole blood (WB) is a suitable matrix for CSA determination. Alternative sampling strategies, such as volumetric absorptive microsampling (VAMS), are novel possibilities for blood collection during TDM for various analytes, including immunosuppressants. This technique is attractive for vulnerable pediatric patients, including home-based self-sampling, remote therapy, and adherence control.
METHODS: This study aimed to develop and validate a new method for CSA determination based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) of WB and VAMS samples. Additionally, these methods were applied for CSA determination in clinical samples from pediatric transplant recipients. A strong point of this study is the assessment of an external proficiency testing scheme.
RESULTS: Both methods were successfully validated within the 1-2000 ng/mL calibration range, with LOD 0.5 and 1 ng/mL for WB and VAMS methods, respectively. All the validation parameters fulfilled the international acceptance criteria for bioanalytical methods. Cross-validation confirmed the interchangeability of the LC-MS/MS method developed in this study.
CONCLUSIONS: This study developed and validated novel methods for CSA determination in whole blood and VAMS using LC-MS/MS. Clinical validation and proficiency testing confirmed their utility in routine clinical practice.

With the development of highly sensitive bioanalytical techniques, the volume of samples necessary for accurate analysis has reduced. Microsampling, the process of obtaining small amounts of blood, has thus gained popularity as it offers minimal-invasiveness, reduced logistical costs and biohazard risks while simultaneously showing increased sample stability and a potential for the decentralization of the approach and at-home self-sampling. Although the benefits of microsampling have been recognised, its adoption in clinical practice has been slow. Several microsampling technologies and devices are currently available and employed in research studies for various biomedical applications. This review provides an overview of the state-of-the-art in microsampling technology with a focus on the latest developments and advancements in the field of microsampling. Research published in the year 2022, including studies (i) developing strategies for the quantitation of analytes in microsamples and (ii) bridging and comparing the interchangeability between matrices and choice of technology for a given application, is reviewed to assess the advantages, challenges and limitations of the current state of microsampling. Successful implementation of microsampling in routine clinical care requires continued efforts for standardization and harmonization. Microsampling has been shown to facilitate data-rich studies and a patient-centric approach to healthcare and is foreseen to play a central role in the future digital revolution of healthcare through continuous monitoring to improve the quality of life.

<b>Background and Objective:</b> Doxorubicin is an anticancer therapy belonging to the anthracycline class, which has clinical activity in breast cancer. Doxorubicin can cause cardiotoxic effects due to the formation of doxorubicinol as its main metabolite. The purpose of this study was to obtain the optimum sample preparation conditions for the analysis of doxorubicin in VAMS and as a form of therapeutic drug monitoring (TDM) in patients with cancer breasts. <b>Materials and Methods:</b> Analyze doxorubicin and doxorubicinol levels with Volumetric Absorptive Microsampling (VAMS) in patients\' cancer breasts receiving doxorubicin in their therapeutic regimen. The sample was analyzed using Ultra Performance Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS). The method uses deep linear range concentrations of 8-200 ng/mL for doxorubicin and 3-100 ng/mL for doxorubicinol. <b>Results:</b> Multiple reaction monitoring (MRM) value set at m/z 544.22>396.9 for doxorubicin; m/z 546.22>398.9 for doxorubicinol and m/z 528.5>362.95 for daunorubicin. The LLOQ value obtained was 8 ng/mL for doxorubicin and 3 ng/mL for doxorubicinol with linearity of 0.9904 for doxorubicin and 0.9902 for doxorubicinol. Analysis results show doxorubicin levels were in the range of 9.47 ng/mL to 87.84 ng/mL and doxorubicinol range between 4.24 and 54.02 ng/mL. <b>Conclusion:</b> Dosage cumulative doxorubicin ranges between 47.93 and 346.09 mg/m²; with this, the risk of cardiomyopathy in the patients surveyed is under 4%, according to the literature.

Background: Clinical dosage of toxic and essential elements in blood is well established and the collection method is still by venipuncture. This method has drawbacks and is not suited for everyone. Volumetric absorptive microsampling (VAMS) has been shown to have advantages over venipuncture. Materials & methods: Using inductively coupled plasma tandem mass spectrometry, a method for quantifying elements in whole blood sampled on VAMS was developed/validated. Method\'s performance was assessed by comparison with whole blood results. Results: Validation and performance assessment tests tend to show that most of the targeted elements provides accurate and reproducible results comparing to a method of reference. Conclusion: Overall, VAMS presents good preliminary results to eventually become an alternative to venipuncture for blood sampling for some trace elements analysis purposes.

UNASSIGNED: Measurement of trough levels for calcineurin inhibitors by venipuncture sampling is a mainstay of patient management in solid organ transplant recipients but challenging in pediatric patients. Volumetric Absorptive Microsampling (VAMS) is a patient-friendly, minimally invasive sampling technique to accurately collect blood. An assay for measurement of tacrolimus in blood using VAMS, coupled with parallel reaction monitoring (PRM) mass spectrometry, was validated in pediatric heart transplant patients.
UNASSIGNED: Tacrolimus was measured by a newly developed high-resolution PRM assay and compared with low-resolution tandem mass spectrometry (MRM). Dried blood samples were collected from pediatric heart transplant patients (n = 35) using VAMS devices and a satisfaction survey was completed by patients/guardians. Tacrolimus concentrations were compared across whole liquid blood, dried blood spots, and capillary blood, and shipping stability determined.
UNASSIGNED: The PRM assay was linear over a range 1-50 ng/mL, similar to MRM but had greater specificity due to reduced background noise. No significant differences in tacrolimus concentrations were observed between VAMS and venous blood. Tacrolimus dried on VAM tips was stable for 14 days and concentrations were unaffected by postal shipping. The variability in two simultaneously collected at-home patient samples was minimal - average concentration difference was 0.12 ± 0.94 ng/mL (p = 0.6) between paired samples.
UNASSIGNED: A high resolution PRM mass spectrometry assay was developed for home-based dried blood collections for therapeutic monitoring of tacrolimus. The advantage of PRM was enhanced specificity and the VAMS devices provided a simple and convenient approach to blood sampling at home in pediatric heart transplant patients.

Dried blood spots (DBS) collected on filter paper such as Guthrie cards are stored for years at room temperature. The assumption is that once dried, the samples remain stable and quantifiable indefinitely since the metabolites these were initially designed to measure, are known for their extended stability. The concentration of other blood proteins such as cytokines, however, are known to vary with storage even in liquid samples stored at -80 °C for extended periods of time. We sought to determine if cytokines are stable for up to 5 months when stored as a dried blood sample using volumetric absorptive microsampling (VAMS) devices. To test this, blood was collected from 4 healthy participants, spiked with recombinant cytokines, and collected into 30 µL VAMS devices. These prepared VAMS devices were stored at room temperature, 4 °C, or -20 °C for up to 5 months and matching VAMS liquid extracts were stored at -80 °C for the same period of time. At each timepoint, the samples were extracted from the VAMS devices and the extracts were analysed by Luminex® for quantification of up to 31 cytokines. These methods were also tested in a remote clinical study over a period of up to 8 months. Cytokine analysis revealed that room temperature, the current standard for DBS and VAMS storage, performed the poorest out of all storage temperatures with significant losses in 13/21 analytes compared to 4 °C at 5 months. Storage at 4 °C or colder performed well for the majority of analytes tested, however out of those, the optimal storage temperature differed for each analyte. There were a small number of analytes that performed poorly regardless of storage conditions and for fractalkine, this was found to be caused by inefficient recovery during extraction. Cytokine concentrations from finger-prick samples were also found to be much more variable that those in venous blood samples. Our results highlight the need to understand the stability of analytes of interest before committing to longitudinal collection and storage of samples in VAMS devices. These data give confidence that storage at 4 °C or colder was beneficial for cytokine stability. Wherein 25/31 cytokines were quantifiably stable at -20 °C when stored for 3 months and 17/21 were quantifiably stable after 5 months when stored at 4 °C.

The objective of this study was to validate a novel assay using the volumetric absorptive microsampling (VAMS) technique combined with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for the determination of the antiseizure medication perampanel in saliva and its clinical applicability in patients with epilepsy. VAMS tips were loaded with 30 μL of saliva and dried for 60 min. Analytes were extracted with methanol. The supernatant was evaporated under a gentle stream of nitrogen and reconstituted with 60 μL of methanol. Separation and quantification were achieved on a monolithic column connected to a mass spectrometer. Calibration curves were linear between 0.5 and 300 ng/mL. Intra- and inter-day accuracy was within 85.6-103.2% and intra-day and inter-day precision did not exceed 12.1%. Perampanel was stable in samples collected by VAMS and stored under different storage conditions. The VAMS-LC-MS/MS method was validated according to internationally accepted criteria and tested in patients with epilepsy who were receiving a combination of perampanel and other antiseizure medications. The method showed adequate bioanalytical performances, holding great potential as an alternative strategy to support domiciliary TDM in patients with epilepsy treated with perampanel according to the simplicity of sample collection.