![]() ![]() In this context, an attractive technique to overcome the conventional venous sampling limits and simplify TDM application is represented by dried blood spot (DBS). Lastly, the applicability and feasibility of performing TDM using microsamples in a real-life home-sampling context is discussed.Īnticancer drugs are notoriously characterized by a low therapeutic index, the introduction of therapeutic drug monitoring (TDM) in oncologic clinical practice could therefore be fundamental to improve treatment efficacy. ![]() The various impacts of deviating hematocrit values on quantitative results are discussed in a separate section as this is a key issue and undoubtedly the most widely discussed issue in the analysis of dried blood microsamples. We focus on sample preparation, analytics, internal standards, dilution of samples, external quality controls, dried blood spot specific validation parameters, stability and blood-to-plasma conversion methods. Different methodological aspects of microsampling-based methods are discussed and applied to TDM of TKIs. Despite the many advantages associated with dried blood microsampling, quantitative analyses are also associated with some specific difficulties. In this review we focus on the different dried blood microsample-based methods that were used for the quantification of TKIs. Additionally, working with dried matrices improves compound stability, resulting in convenient and cost-effective transport and storage of the samples. The collection of small sample volumes is especially relevant for use in pediatric populations or in pharmacokinetic studies. Collection of samples via finger-prick is minimally invasive and considered convenient and simple, enabling sampling by the patients themselves in their home-setting. The use of dried blood microsamples can overcome these limitations. However, the use of plasma poses some challenges related to sampling and stability. Plasma, obtained via traditional venous blood sampling, is the standard matrix for TDM of TKIs. Moreover, most of the available TKIs are susceptible to various drug-drug interactions and medication adherence can be checked by performing TDM. TKIs are perfect candidates for TDM as they show a relatively small therapeutic window, a wide inter-patient variability in pharmacokinetics and a correlation between drug concentration and effect. Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) is not yet performed routinely in the standard care of oncology patients, although it offers a high potential to improve treatment outcome and minimize toxicity. ![]() ![]() EPC: Estimated plasma concentration Hct: Hematocrit IM: Imatinib. Dashed lines indicate IM target concentrations in plasma to therapeutic drug monitoring (1000 ng ml -1 ) and proposed IM concentration target. (C) (i) Bland and Altman plot comparing IM EPC calculated from DBS levels and correction factor with measured plasma concentrations (ii) correlation between EPC calculated from DBS levels and correction factor and measured plasma concentrations. (B) (i) Bland and Altman plot comparing IM EPC calculated from DBS levels and Hct with measured plasma concentrations (ii) correlation between EPC calculated from DBS levels and correction factor and measured plasma concentrations. (A) (i) Bland and Altman plot comparing IM concentrations in DBS with measured plasma concentrations (ii) correlation between IM concentrations in DBS and measured plasma concentrations. Comparison of imatinib concentrations in DBS and concentrations in plasma estimated from dried blood with measured concentrations in plasma in clinical samples. ![]()
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My apologies for the delay, as I was catching up on our Olympic Trials coverage and travel back from Oregon to California. ![]() ![]() ![]() INFO 13:24:14.751 Loading MediaInfo library INFO 13:24:14.507 Checking shared folder: H:\VideosĭEBUG 13:24:14.515 Reading disable_subtitles: default: false, current: true INFO 13:24:14.268 Web conf permissions: file not foundĭEBUG 13:24:14.313 Reading auto_update: default: false, current: trueĭEBUG 13:24:14.456 Reading hostname: default: null, current: “192.168.1.70”ĭEBUG 13:24:14.476 Reading network_interface: default: “”, current: “eth3”ĭEBUG 13:24:14.483 Reading renderer_force_default: default: false, current: trueĭEBUG 13:24:14.486 Reading renderer_default: default: “”, current: “PlayStation 3”ĭEBUG 13:24:14.507 Reading folders: default: “”, current: “H:\Videos” INFO 13:24:14.268 Web conf path: C:\ProgramData\PMS\WEB.conf INFO 13:24:14.268 Profile permissions: rw INFO 13:24:14.268 Profile path: C:\ProgramData\PMS\PMS.conf INFO 13:24:14.267 Profile directory permissions: rw INFO 13:24:14.265 Profile directory: C:\ProgramData\PMS INFO 13:24:14.265 Logging config file: D:\PS3 Media Server\logback.xml INFO 13:24:14.265 Temp directory: C:\Users\Client\AppData\Local\Temp\ps3mediaserver INFO 13:24:14.262 Working directory: D:\PS3 Media Server INFO 13:24:14.258 Java: Java HotSpot(TM) 64-Bit Server VM 1.7.0_25 by Oracle Corporation It should be able to see your DLNA clients now.ĭid not work for me. 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Note: Please replace the âqqqâ behind â-srcaliasâ with the alias, you noted in the previous step and the âxxxâ behind â-deststorepassâ with the password for the .jks file. The last step is now to import the certificate and its private key into the keystore by running the following command: keytool -importkeystore -srckeystore d:\cert\wildcard.pfx -srcstoretype pkcs12 -srcalias -destkeystore d:\cert\wildcard.jks -deststoretype jks -deststorepass xxx -destalias wildcard Open the file cert.txt and look for the line starting with â Aliasname:â. To do so, run the following command: keytool -v -list -storetype pkcs12 -keystore d:\cert\wildcard.pfx > d:\cert\cert.txt In order to import the certificate, we first have to reveal the alias used. Now we import the other two CA certificates the same way: keytool -import -trustcacerts -file "d:\cert\COMODORSAAddTrustCA.crt" -alias COMODORSAAddTrustCA -keystore d:\cert\wildcard.jks -storepass xxx keytool -import -trustcacerts -file "d:\cert\COMODORSAOrganizationValidationSecureServerCA.crt" -alias COMODORSAOrganizationValidationSecureServerCA -keystore d:\cert\wildcard.jks -storepass xxx Note: Please replace the âxxxâ behind â-storepassâ with a reasonable password. Since the key store doesnât exist, it will create it automatically: keytool -import -trustcacerts -file "d:\cert\AddTrustExternalCARoot.crt" -alias AddTrustExternalCARoot -keystore d:\cert\wildcard.jks -storepass xxx The first command puts the root CAâs certificate into the keystore. Now, weâll use the keytool command inside the java installation folder (in my case C:\Program Files\Java\jre1.8.0_201\bin to create the keystore and put all necessary files in there.
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