This study aimed to develop a UPLC-MS/MS method for determining plasma levels of L-aspartic acid and L-asparagine and the activity of L-asparaginase. L-aspartic acid, L-asparagine, and L-aspartic acid-2,3,3-d3 were extracted from human plasma by protein precipitation with sulfosalicylic acid (30%, v/v). The plasma samples were analyzed using an Imtakt Intrada amino acid analysis column with 25 mM ammonium formate and 0.5% formic acid in acetonitrile as the mobile phase with step gradient method at a flow rate of 0.5 mL/min. The injection volume was 5 µL, and the total run time was 15 min. Inter- and intra-batch accuracies (%) ranged from 96.62–106.0% for L-aspartic acid and 89.85–104.8%, for L-asparagine, and the coefficient of variation (CV%) did not exceed 7%. The validation results for L-aspartic acid and L-asparagine satisfied the specified criterion, however, the results for L-asparaginase activity assay showed a borderline validity. This study could be a foundation for further development of therapeutic drug monitoring systems using UPLC-MS/MS.
Ammonium Compounds ; Asparagine ; Aspartic Acid ; Drug Monitoring ; Humans ; Methods ; Plasma

Drug Monitoring ; Humans ; Immunosuppressive Agents ; administration & dosage ; Liver Transplantation ; methods

Therapeutic drug monitoring (TDM) is the clinical practice of measuring specific drugs at designated intervals to maintain a constant concentration in a patient's bloodstream, thereby optimizing individual dosage regimens. It is unnecessary to employ TDM for the majority of medications, and it is used mainly for monitoring drugs with narrow therapeutic ranges, drugs with marked pharmacokinetic variability, medications for which target concentrations are difficult to monitor, and drugs known to cause therapeutic and adverse effects. The process of TDM is predicated on the assumption that there is a definable relationship between dose and plasma or blood drug concentration, and between concentration and therapeutic effects. TDM begins when the drug is first prescribed, and involves determining an initial dosage regimen appropriate for the clinical condition and such patient characteristics as age, weight, organ function, and concomitant drug therapy. When interpreting concentration measurements, factors that need to be considered include the sampling time in relation to drug dose, dosage history, patient response, and the desired medicinal targets. The goal of TDM is to use appropriate concentrations of difficult-to-manage medications to optimize clinical outcomes in patients in various clinical situations.
Algorithms ; Dose-Response Relationship, Drug ; Drug Monitoring/*methods/trends ; Forecasting ; Humans ; Patient Compliance ; Pharmacokinetics

The development of automatic drug delivery is reviewed in this paper. The control-relevance of models, the relevant algorithm, the system running and the simulation effect are introduced. The value for clinical application of each case is assessed. The new advances and high-lights of researches are discussed.
Algorithms ; Drug Delivery Systems ; instrumentation ; Drug Therapy, Computer-Assisted ; instrumentation ; Humans ; Infusion Pumps ; Monitoring, Physiologic ; methods

Animals ; Chromatography, Supercritical Fluid ; methods ; Drug Monitoring ; methods ; Environmental Pollutants ; analysis ; Forensic Medicine ; methods ; Humans ; Substance-Related Disorders ; diagnosis

OBJECTIVETo explore the biomarkers for monitoring trinitrotoluene (TNT) exposure, the relationship between TNT hemoglobin adducts and TNT exposed level.

METHODHemoglobin adducts (4A-Hb and 2A-Hb) were determined by GC-MS in 25 TNT exposed workers. TNT exposed level was evaluated by determining skin contaminated and inhaled TNT levels. The correlation between hemoglobin adducts level and TNT exposed level was analyzed.

RESULTSThere was a correlation between total TNT exposure level, especially skin exposure level, and 4A-Hb or 2A-Hb content. No significant difference was found between the slopes and intercepts of lin ear equation of (4A-Hb) vs TNT exposed level and linear equation of (4A-Hb +2A-Hb) vs TNT exposed level (P > 0.05).

CONCLUSIONSkin contamination is the major role of TNT exposure. TNT exposed level can be evaluated by determining the content of both 4A-Hb and 2A-Hb, and 4A-Hb is more suitable for monitoring TNT exposure.

Environmental Monitoring ; methods ; Hemoglobins ; metabolism ; Humans ; Occupational Exposure ; Skin ; drug effects ; Trinitrotoluene ; metabolism

BACKGROUND: The immunosuppressant drugs (ISDs), tacrolimus and cyclosporine, are vital for solid organ transplant patients to prevent rejection. However, toxicity is a concern, and absorption is highly variable across patients; therefore, ISD levels need to be precisely monitored. In the Asia-Pacific (APAC) region, tacrolimus and cyclosporine concentrations are typically measured using immunoassays. The objective of this study was to assess the analytical performance of Roche Elecsystacrolimus and cyclosporinee electrochemiluminescence immunoassays (ECLIAs). METHODS: This evaluation was performed in seven centers across China, South Korea, and Malaysia. Imprecision (repeatability and reproducibility), assay accuracy, and lot-to-lot reagent variability were tested. The Elecsys ECLIAs were compared with commercially available immunoassays (Architect, Dimension, and Viva-E systems) using whole blood samples from patients with various transplant types (kidney, liver, heart, and bone marrow). RESULTS: Coefficients of variation for repeatability and reproducibility were ≤5.4% and ≤12.4%, respectively, for the tacrolimus ECLIA, and ≤5.1% and ≤7.3%, respectively, for the cyclosporine ECLIA. Method comparisons of the tacrolimus ECLIA with Architect, Dimension, and Viva-E systems yielded slope values of 1.01, 1.14, and 0.897, respectively. The cyclosporine ECLIA showed even closer agreements with the Architect, Dimension, and Viva-E systems (slope values of 1.04, 1.04, and 1.09, respectively). No major differences were observed among the different transplant types. CONCLUSIONS: The tacrolimus and cyclosporine ECLIAs demonstrated excellent precision and close agreement with other immunoassays tested. These results show that both assays are suitable for ISD monitoring in an APAC population across a range of different transplant types.
Absorption ; China ; Cyclosporine* ; Drug Monitoring ; Heart ; Humans ; Immunoassay* ; Korea ; Liver ; Malaysia ; Methods ; Tacrolimus* ; Transplants

OBJECTIVETo explore a sampling method which could reflect iodine deficiency disorders (IDD) status at provincial level and discover risk areas with non-iodized salt problem.

METHODBaseline data of Iodized salt from Gansu and Fujian provinces were analyzed with Monte Carlo method both at county and prefecture levels respectively. True positive rate and false positive rate were also calculated.

RESULTSWith data from 7 - 8 villages or 4 - 5 townships counties at risk could be discovered. The true positive rate was around 80% and false positive rate was around 20%. At prefecture level, when randomly selecting and checking 3 counties, the samples would satisfy the discovery of all the risk areas with non-iodized salt problem.

CONCLUSIONSWe suggested that the sampling method of iodized salt investigation in national IDD surveillance as follows: to randomly choose 3 counties at each prefecture, 4 townships at each county, 2 villages at each township and 10 salt samples by household survey. The coverage rate of iodized salt in a province could be calculated by post-weighted method with population number.

China ; Drug Monitoring ; methods ; Humans ; Iodine ; deficiency ; pharmacology ; Monte Carlo Method ; Sodium Chloride, Dietary ; pharmacology

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

This paper presents a microcontroller system for target controlled infusion according to pharmacodynamic parameters of intravenous anesthetics. It can control the depth of anesthesia by adjusting the level of plasma concentrations. The system has the advantages of high precision, extending power and easy manipulation. It has been used in the clinical anesthesia.
Anesthesia, Intravenous ; instrumentation ; methods ; Anesthetics, Intravenous ; administration & dosage ; pharmacokinetics ; Drug Delivery Systems ; methods ; Drug Therapy, Computer-Assisted ; methods ; Humans ; Monitoring, Intraoperative ; methods