scholarly journals Integrated Microfluidic Devices Fabricated in Poly (Methyl Methacrylate) (PMMA) for On-site Therapeutic Drug Monitoring of Aminoglycosides in Whole Blood

Biosensors ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 19 ◽  
Author(s):  
Zaidon Al-aqbi ◽  
Yiing Yap ◽  
Feng Li ◽  
Michael Breadmore
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Methyl Methacrylate ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Bacterial Infections ◽  
Aminoglycoside Antibiotic ◽  
Therapeutic Drug ◽  
Poly Methyl Methacrylate ◽  
Antibiotic Drugs ◽  
Auditory Dysfunction

On-site therapeutic drug monitoring (TDM) is important for providing a quick and accurate dosing to patients in order to improve efficacy and minimize toxicity. Aminoglycosides such as amikacin, gentamicin, and tobramycin are important antibiotics that have been commonly used to treat infections of chronic bacterial infections in the urinary tract, lung, and heart. However, these aminoglycosides can lead to vestibular and auditory dysfunction. Therefore, TDM of aminoglycosides is important due to their ototoxicity and nephrotoxicity. Here, we have developed a hot embossed poly (methyl methacrylate) (PMMA) microfluidic device featuring an electrokinetic size and mobility trap (SMT) to purify, concentrate, and separate the aminoglycoside antibiotic drugs amikacin, gentamicin, and tobramycin. These drugs were separated successfully from whole blood within 3 min, with 30-fold lower detection limits compared to a standard pinched injection. The limit of detections (LOD) were 3.75 µg/mL for gentamicin, 8.53 µg/mL for amikacin, and 6.00 µg/mL for tobramycin. These are sufficient to cover the therapeutic range for treating sepsis of 6–10 μg/mL gentamicin and tobramycin and 12–20 μg/mL of amikacin. The device is simple and could be mass produced via embossing or injection molding approaches.

Therapeutic Drug Monitoring of Antibiotic Drugs

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Maria Shipkova ◽  
Hedi Jamoussi
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Antibiotic Drugs

scholarly journals Therapeutic Drug Monitoring of Protein Unbound Ciprofloxacin Concentrations to avoid inadequate Treatment of severe Bacterial Infections in Critically ill Patients

2018 ◽  
Vol 4 (5) ◽  
pp. 166-174
Author(s):  
Nora J mabelis ◽  
Kimberly N. Shudofsky ◽  
Joost J. van Raaij ◽  
Sjoerd D. Meenks ◽  
Thomas Havenith ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Bacterial Infections ◽  
Therapeutic Drug

scholarly journals Routine clinical monitoring of sirolimus (rapamycin) whole-blood concentrations by HPLC with ultraviolet detection

1996 ◽  
Vol 42 (12) ◽  
pp. 1943-1948 ◽  
Author(s):  
K L Napoli ◽  
B D Kahan
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Clinical Status ◽  
Reversed Phase ◽  
Therapeutic Drug ◽  
Full Time ◽  
Limit Of Quantification ◽  
Blood Concentrations ◽  
Ultraviolet Detection

Abstract During phase I/II clinical trials of sirolimus (rapamycin; SRL), therapeutic drug monitoring was performed with a multistep liquid-liquid extraction of 1-mL aliquots of whole blood followed by reversed-phase HPLC with ultraviolet detection. Blood was sampled according to a standardized protocol and clinical status. SRL concentrations were interpolated from calibration curves with a linear range of 0-50 micrograms/L and 1 microgram/L lower limit of quantification. Quality control was monitored over 68 consecutive analytical runs by using frozen aliquots of SRL-supplemented pooled whole blood at 4, 12, and 32 micrograms/L. These samples showed mean concentrations of 3.7 +/- 0.6, 10.9 +/- 1.1, and 29.6 +/- 2.6 micrograms/L, respectively. This method for therapeutic drug monitoring of SRL permits one full-time technician to analyze 100 clinical specimens per week with a 24-h turnaround time. With this method, a strong linear relation (r2 = 0.946, Sy/x = 0.41, n = 115) between the average SRL concentration over a 24-h period and the SRL concentration at the 24th h was revealed.

Plasma vs whole blood for therapeutic drug monitoring of patients receiving FK 506 for immunosuppression

1994 ◽  
Vol 40 (12) ◽  
pp. 2247-2253 ◽  
Author(s):  
M Winkler ◽  
B Ringe ◽  
J Baumann ◽  
M Loss ◽  
K Wonigeit ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Enzyme Immunoassay ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Plasma Concentrations ◽  
Therapeutic Monitoring ◽  
Therapeutic Drug ◽  
Fk 506 ◽  
Blood Samples ◽  
The Matrix

Abstract By retrospective analysis of 13,000 blood samples obtained from 248 patients receiving FK 506 therapy, we compared the suitability of plasma with that of whole blood as the matrix for therapeutic drug monitoring of FK 506. The plasma concentrations did not correlate with the concentrations in whole blood (r = 0.56). In contrast to plasma samples (analyzed by enzyme immunoassay), FK 506 was detectable in all whole-blood samples (analyzed by enzyme immunoassay/microparticle enzyme immunoassay). The inter- and intraindividual variations of FK 506 measurements were greater in plasma than in whole blood. Moreover, plasma concentrations correlated only poorly with clinical events. There was a tendency to greater plasma concentrations being measured during episodes of toxicity, but no clear difference was evident between stable course and rejection. In whole-blood specimens, a correlation between reduced or increased FK 506 concentrations and rejection or toxicity, respectively, was observed. The discriminatory power of whole-blood values was greater for the differentiation between toxicity and stable course than between rejection and stable course. We therefore recommend whole blood rather than plasma as the matrix for therapeutic monitoring of FK 506 concentrations.

scholarly journals Therapeutic Drug Monitoring: Performance of a FRET-Based Point-Of-Care Immunoassay for the Quantitation of Infliximab and Adalimumab in Blood

2020 ◽  
Author(s):  
Edgar Ong ◽  
Ruo Huang ◽  
Richard Kirkland ◽  
Stefan Westin ◽  
Jared Salbato ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Point Of Care ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Drug Level ◽  
Analytical Performance ◽  
Quantitative Detection ◽  
Therapeutic Drug

<p>Two fast (<5 min), time-resolved fluorescence resonance energy transfer (FRET)-based immunoassays (Procise IFX™ and Procise ADL™) were developed for the quantitative detection of infliximab (IFX), adalimumab (ADL), and their respective biosimilars for use in therapeutic drug monitoring (TDM) using 20 µL of finger prick whole blood at the point-of-care or whole blood/serum in a central lab. Studies were performed to characterize analytical performance of the Procise IFX and the Procise ADL assays on the ProciseDx™ analyzer.</p> <p><br></p><p>The Procise IFX and Procise ADL assays both showed good analytical performance with respect to sensitivity, specificity, linearity, and precision suitable for routine clinical use as well as excellent correlation to current commercial ELISA IFX and ADL measurement methods.</p> <p><br></p><p>Results indicated that the Procise IFX and Procise ADL assays are sensitive, specific, and precise yielding results in less than 5 minutes from either whole blood or serum. This indicates the Procise IFX and Procise ADL assays are useful for obtaining fast and accurate IFX or ADL quantitation, thus avoiding delays inherent to current methods and enabling immediate drug level dosing decisions to be made during a single patient visit.</p>

scholarly journals Effect of sample heating on results of therapeutic drug monitoring

2021 ◽  
Vol 45 (3) ◽  
pp. 183-187
Author(s):  
Dao-Hai Cheng ◽  
Zhen-Guang Huang ◽  
Jing-Bing Zhu
Keyword(s):  
Heat Treatment ◽  
Valproic Acid ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Plasma Heating ◽  
Therapeutic Drug ◽  
Blood Concentrations ◽  
Therapeutic Drugs ◽  
Drug Concentrations

Abstract Objectives Heat treatment is a convenient measure for pathogens inactivation. The authors investigated the effects of this method on blood concentrations of six commonly therapeutic drugs. Methods Plasma and whole blood were pretreated with or without heating at 56 °C for 30 min, and drug concentrations of vancomycin, methotrexate, valproic acid, digoxin, carbamazepine, and cyclosporine were examined. Results Increased valproic acid levels after plasma heating (63.2 ± 30.2 vs. 62.1 ± 29.8 mg/L, mean recovery 102.0%) and whole blood heating (64.5 ± 30.5 vs. 62.1 ± 29.8 mg/L, mean recovery 104.6%) were observed (both p<0.05), but these differences were not considered clinically important. Recoveries of vancomycin in heat treatments varied widely, with an average and significant decrease of 15.8% in value after whole blood heating (11.7 ± 8.1 vs. 13.7 ± 8.6 mg/L, p<0.05). Conclusions Plasma or whole blood heating at 56 °C for 30 min are feasible in pathogens inactivation during monitoring methotrexate, valproic acid, digoxin, carbamazepine, and cyclosporine. However, such pretreatment seems inappropriate in monitoring vancomycin concentrations. Those results highlight the need for caution when applying heat treatment for pathogens inactivation in therapeutic drug monitoring.

Volumetric Microsampling of Capillary Blood Spot vs Whole Blood Sampling for Therapeutic Drug Monitoring of Tacrolimus and Cyclosporin A: Accuracy and Patient Satisfaction

2020 ◽  
Vol 5 (3) ◽  
pp. 516-530
Author(s):  
Michael M Mbughuni ◽  
Maria A Stevens ◽  
Loralie J Langman ◽  
Yogish C Kudva ◽  
William Sanchez ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Cyclosporin A ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Solid Phase ◽  
Venous Blood ◽  
Therapeutic Drug ◽  
Blood Collection ◽  
Clinical Validation ◽  
Transplant Patients

Abstract Background Immunosuppressant therapeutic drug monitoring (TDM) usually requires outpatient travel to hospitals or phlebotomy sites for venous blood collection; however Mitra® Microsampling Device (MSD) sampling could allow self-collection and shipping of samples to a laboratory for analysis. This study examined the feasibility of using volumetric microsampling by MSD for TDM of tacrolimus (TaC) and cyclosporin A (CsA) in transplant patients, along with their feedback on the process. Methods MSD was used to collect TaC and CsA from venous (VB) or capillary (CB) blood. The MSDs were rehydrated, extracted, and analyzed using on-line solid phase extraction coupled to tandem mass spectrometry (SPE-MS/MS). We report an abbreviated method validation of the MSD including: accuracy, precision, linearity, carry-over, and stability using residual venous whole blood (VB) samples. Subsequent clinical validation compared serially collected MSD + CB against VB (200 µL) from transplant patients. Results Accuracy comparing VB vs. MSD+VB showed high clinical concordance (TaC = 89% and CsA = 98%). Inter- and intra-precision was ≤11.5 %CV for TaC and CsA. Samples were stable for up to 7 days at room temperature with an average difference of &lt;10%. Clinical validation with MSD+CB correlated well with VB for CsA (slope = 0.95, r2 = 0.88, n = 47) and TaC (slope = 0.98, r2 = 0.82, n = 49). CB vs. VB gave concordance of 94% for CsA and 79% for TaC. A satisfaction survey showed 82% of patients preferred having the capillary collection option. Conclusion Transplant patients favored having the ability to collect capillary samples at home for TaC/CsA monitoring. Our results demonstrate good concordance between MSD+CB and VB for TaC and CsA TDM, but additional studies are warranted.

Rapid analysis of whole blood by paper spray mass spectrometry for point-of-care therapeutic drug monitoring

The Analyst ◽  
2012 ◽  
Vol 137 (10) ◽  
pp. 2344 ◽  
Author(s):  
Ryan D. Espy ◽  
Nicholas E. Manicke ◽  
Zheng Ouyang ◽  
R. Graham Cooks
Keyword(s):  
Mass Spectrometry ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Point Of Care ◽  
Rapid Analysis ◽  
Therapeutic Drug ◽  
Paper Spray
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