How does the determination of plasma endogenous uracil and dihydrouracil levels differ in various clinical settings?5 answersThe determination of plasma endogenous uracil (U) and dihydrouracil (DHU) levels varies across clinical settings. Studies have shown that measuring U plasma concentrations can serve as a surrogate for dihydropyrimidine dehydrogenase (DPD) activity. This is crucial before initiating fluoropyrimidine (FP) chemotherapy to prevent severe toxicity. While traditional methods involve phlebotomy, innovative devices like Tasso-SST® allow for small blood samples from skin capillaries, simplifying the process. Additionally, the correlation between plasma uracil values and DPD deficiency is being explored to optimize treatment balance between efficacy and toxicity. Endogenous U and DHU measurements, adjusted for renal function, have shown promise in predicting severe fluoropyrimidine toxicity, outperforming genotyping for DPYD variants. A bioanalytical method has been developed for simultaneous U and 5-FU determination in plasma, aiding in phenotyping before FP treatment.
Why serum analytes may be a good option for diagnosing bladder cancer?4 answersSerum analytes are a promising option for diagnosing bladder cancer due to their ability to differentiate between cancer patients and non-cancer controls, as well as between different grades and stages of bladder cancer. Studies have identified specific serum metabolites and miRNAs that exhibit significant differences in abundance between bladder cancer patients and healthy individuals, leading to the development of diagnostic signatures with high sensitivity and specificity. These serum biomarkers offer a non-invasive and easily accessible method for detecting bladder cancer, potentially facilitating early diagnosis and timely intervention, which are crucial for improving patient outcomes and prognosis. The use of serum analytes as diagnostic markers holds promise for enhancing the efficiency and effectiveness of bladder cancer detection and management.
Therapeutic drug monitoring of 6-mercaptopurine in plasma?4 answersTherapeutic drug monitoring (TDM) of 6-mercaptopurine (6-MP) in plasma is important for maintaining the efficacy and safety of the drug in patients with inflammatory bowel disease (IBD). Various methods have been proposed for the determination of 6-MP in plasma, including high-performance liquid chromatography (HPLC). HPLC methods have been shown to be sensitive, specific, accurate, and precise for the quantification of 6-MP in human plasma. Additionally, gold colloidal solutions have been investigated as surface-enhanced Raman scattering (SERS) platforms for the detection and quantitative analysis of 6-MP. SERS-based assays have shown promise for TDM of 6-MP, with a linearity range of 1-15 μM and a limiting sensitivity (LOD) of 1.0 μM. Measurement of red cell 6-MP metabolites, such as 6-thioguanine nucleotide (TGN) and methylmercaptopurine metabolites (MeMPs), can also be used to monitor therapy in children with childhood lymphoblastic leukemia. Overall, these methods provide valuable tools for the TDM of 6-MP in plasma.
How can urine FTIR be used to detect bladder cancer?5 answersUrine FTIR can be used to detect bladder cancer by analyzing the attenuated total refraction Fourier transform infrared (ATR-FTIR) spectra of urine samples. This spectroscopic method allows for the rapid detection of non-muscle invasive bladder cancer (NMIBC) recurrence in urine. The technique involves collecting urine samples from previously-diagnosed NMIBC patients and acquiring ATR-FTIR spectra directly from the urine samples. The spectra are then processed and normalized using parameter grid searching. Machine learning models, such as Regularized Random Forests (RRF), can be applied to the processed spectra to classify the samples as cancer-free or recurrence. The performance of the RRF model achieved a 0.92 area under the receiver operating characteristic (AUROC) with 86% sensitivity and 77% specificity. This spectroscopic liquid biopsy approach provides a promising and less invasive technique for the early identification of NMIBC.
How to analyze dapivirine concentration?5 answersDapivirine concentration can be analyzed using various methods. One method is liquid chromatography-tandem mass spectrometry (LC-MS/MS), which has been used to quantify dapivirine in breast milk samples from lactating women. Another method is high-performance liquid chromatography (HPLC) with UV detection, which has been used to assay dapivirine in different biological matrices such as cell lysates, receptor media, and mucosal tissues. In both methods, the samples are processed and subjected to analysis using specific instruments. The LC-MS/MS method has an analytical measuring range of 10-1000 pg/mL and has been validated according to FDA guidelines. The HPLC method with UV detection has a linear range of 0.02-1.5 μg/mL and has been validated for in vitro and ex vivo experiments. These methods provide accurate and precise quantification of dapivirine concentration, allowing for the assessment of drug efficacy and distribution in different biological samples.
How to determine the solubility of an oral drug in serum?5 answersThe solubility of an oral drug in serum can be determined using various methods. One approach is to use smart systems, which are considered more reliable and important in this field. Another method is to evaluate the permeability of the drug across the gastrointestinal membrane, as oral absorption is influenced by both dissolution and permeability. Mathematical models have also been developed to correlate and predict the solubility of drugs, providing a faster and easier tool for solubility determination. Additionally, computational models can be used to predict water solubility, which is an important factor for successful drug development. By comparing calculated and measured solubility, the value of these models can be assessed, although their limitations should be considered. Overall, a combination of experimental, mathematical, and computational methods can be employed to determine the solubility of an oral drug in serum.