The right blood collection tube for therapeutic drug monitoring and toxicology screening procedures: Standard tubes, gel or mechanical separator?

Abstract Background Some therapeutic drugs are unstable during sample storage in gel tubes. BD Vacutainer® Barricor™ Plasma Blood Collection Tube with nongel separator was compared with plasma gel tubes, BD Vacutainer PST™, PST II, and BD Vacutainer Serum Tube for acetaminophen, salicylate, digoxin, carbamazepine, phenytoin, valproic acid, and vancomycin during sample storage for up to 7 days. Methods Seven hospital sites enrolled 705 participants who were taking at least one selected drug. The study tubes were collected and tested at initial time (0 h), after 48 h of storage at room temperature and on day 7 (after additional 5 days of refrigerated storage). The performance of BD Barricor tube was evaluated for each drug by comparing BD Barricor samples with samples from the other tubes at 0 h from the same participant; stability was evaluated by comparing test results from the same tube at 0 h, 48 h, and 7 days. Results At 0 h, BD Barricor showed clinically equivalent results for selected therapeutic drugs compared with the other tubes, except phenytoin in BD PST. Phenytoin samples ≥20 µg/mL in BD PST had 10–12% lower values than samples in BD Barricor. During sample storage, all selected drugs remained stable for 7 days in BD Barricor and in serum aliquots. In BD PST, all drugs remained stable except phenytoin and carbamazepine and in BD PST II except for phenytoin. Conclusion The BD Barricor Tube is effective for the collection and storage of plasma blood samples for therapeutic drug monitoring without sample aliquoting.

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

The Journal of Applied Laboratory Medicine ◽

10.1093/jalm/jfaa005 ◽

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 <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.

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The Right Dose: From Phase I to Clinical Practice

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_319567 ◽

2021 ◽

pp. 92-106

Author(s):

Stefanie L. Groenland ◽

Mark J. Ratain ◽

Lisa S. Chen ◽

Varsha Gandhi

Keyword(s):

Clinical Practice ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Kinase Inhibitors ◽

Optimal Dose ◽

Therapeutic Drug ◽

Full Potential ◽

Drug Dosing ◽

Anticancer Treatment ◽

The Right

To realize the full potential of promising new anticancer drugs, it is of paramount importance to administer them at the right dose. The aim of this educational article is to provide several opportunities to optimize anticancer drug dosing, focusing on oral targeted therapies. First, therapeutic drug monitoring can optimize exposure in individual patients, if the optimal concentration is known. This approach is of particular interest in regard to oral kinase inhibitors with high interindividual pharmacokinetic variability. If exposure is related to response, then therapeutic drug monitoring is potentially feasible, although the clinical utility of this approach has not yet been established. Other approaches to reduce variability include administration of more frequent, smaller doses and administration under optimal prandial conditions. However, for many drugs, the labeled dose has not been demonstrated to be the optimal dose; for such agents, the vast majority of patients may be receiving excessive doses, which results in excessive toxicity. Furthermore, administration of lower off-label doses may reduce both medical and financial toxicity. These strategies should be applied from registration studies to clinical practice, with the goal of better optimizing anticancer treatment.

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Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks

Microorganisms ◽

10.3390/microorganisms8030415 ◽

2020 ◽

Vol 8 (3) ◽

pp. 415 ◽

Cited By ~ 2

Author(s):

Stefan Felix Ehrentraut ◽

Stefan Muenster ◽

Stefan Kreyer ◽

Nils Ulrich Theuerkauf ◽

Christian Bode ◽

...

Keyword(s):

Renal Function ◽

Therapeutic Drug Monitoring ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Plasma Levels ◽

Therapeutic Drug ◽

The Right ◽

The Impact ◽

Current Guidelines

(1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR/PDR pathogens. Although new guidelines with detailed recommendations for Colistin dosing are available, finding the right dose in critically ill patients with renal failure remains difficult. Here, we evaluate the efficiency of the current guidelines’ recommendations by using high resolution therapeutic drug monitoring of Colistin. (2) Methods: We analyzed plasma levels of Colistin and its prodrug colisthimethate sodium (CMS) in 779 samples, drawn from eight PDR-infected ICU patients, using a HPLC-MS/MS approach. The impact of renal function on proper Colistin target levels was assessed. (3) Results: CMS levels did not correlate with Colistin levels. Over-/Underdosing occurred regardless of renal function and mode of renal replacement therapy. Colistin elimination half-time appeared to be longer than previously reported. (4) Conclusion: Following dose recommendations from the most current guidelines does not necessarily lead to adequate Colistin plasma levels. Use of Colistin without therapeutic drug monitoring might be unsafe and guideline adherence does not warrant efficient target levels in critically ill patients.

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Therapeutic drug monitoring of anti-epileptic drugs – a clinical verification of volumetric absorptive micro sampling

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2019-0784 ◽

2020 ◽

Vol 58 (5) ◽

pp. 828-835 ◽

Cited By ~ 1

Author(s):

Thierry P.I.J.M. Canisius ◽

J.W.P. Hans Soons ◽

Pauline Verschuure ◽

Emmeke A. Wammes-van der Heijden ◽

Rob P.W. Rouhl ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Whole Blood ◽

Storage Temperature ◽

Vulnerable Groups ◽

Therapeutic Drug ◽

Blood Collection ◽

Accurate Detection ◽

The Stability ◽

The Impact

AbstractBackgroundTherapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) can serve as a valuable tool in optimising and individualising epilepsy treatment, especially in vulnerable groups such as pregnant women, the elderly and children. Unfortunately, TDM is often performed suboptimally due to limitations in blood collection. Therefore, we investigated volumetric absorptive micro sampling (VAMS) – a new home-sampling technique. We aimed to evaluate VAMS to determine and quantify the different AEDs and concentrations of 16 different AEDs in whole blood collected by VAMS.MethodsPatient blood samples (n = 138) were collected via venepunctures at the Academic Centre for Epileptology Kempenhaeghe. AED concentrations were determined, and these concentrations were used to compare the VAMS method (whole blood) with the conventional method (serum). In addition, the recovery was examined as well as the impact of haematocrit. Finally, AED-spiked blood was used to test the stability of the AEDs inside the micro-sampler devices over a period of time and whether temperature had an effect on the stability.ResultsVAMS allows for an accurate detection of 16 different AEDs within 2 days after sampling. Deviation in recovery was less than 10% and high correlations were found between VAMS and conventional sampling. Moreover, haematocrit does not have an effect with values between 0.3 and 0.5 (L/L). Finally, although storage temperature of VAMS does affect some AEDs, most are unaffected.ConclusionsVAMS enables an accurate detection of a wide variety of AEDs within 2 days after sampling.

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Analytical and Sample Preparation Protocol for Therapeutic Drug Monitoring of 12 Thiopurine Metabolites Related to Clinical Treatment of Inflammatory Bowel Disease

Molecules ◽

10.3390/molecules23071744 ◽

2018 ◽

Vol 23 (7) ◽

pp. 1744 ◽

Cited By ~ 3

Author(s):

Daniel Pecher ◽

Svetlana Dokupilová ◽

Zuzana Zelinková ◽

Maikel Peppelenbosch ◽

Jana Lučeničová ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Sample Preparation ◽

Drug Monitoring ◽

Preparation Procedure ◽

Clinical Samples ◽

Therapeutic Drug ◽

Blood Collection ◽

Esi Ms ◽

Sample Preparation Procedure ◽

Inflammatory Bowel

Thiopurines (TP) represent an important therapeutic tool for the treatment of inflammatory bowel diseases (IBD) in the current situation of rising incidence and health care costs. The results of multiple clinical studies aimed at finding correlations between levels of TP metabolites and response of IBD patients to the treatment are, however, often controversial due to variability in analytical and sample preparation procedures among these studies. In this work, therefore, an updated analytical and sample preparation procedure for therapeutic drug monitoring (TDM) of TP metabolites in blood samples obtained from patients with IBD was proposed to establish a unified protocol. An advanced analytical method based on ion-exchange liquid chromatography hyphenated with tandem mass spectrometry (IEC-ESI-MS/MS) was used for the determination of the profiles of 12 individual TP metabolites in the particular steps of sample preparation procedure including blood collection, red blood cells (RBC) isolation, lysis, and storage. Favorable performance parameters of the IEC-ESI-MS/MS method (LLOQs 1–10 nmol/L, accuracy 95–105%, intra-day and inter-day precision < 10%, selectivity demonstrated via no sample matrix interferences) and acceptable stability (peak area fluctuations < 15%) of clinical samples under the proposed sample preparation conditions {(i) EDTA anticoagulant tube for the blood collection; (ii) 4 °C and 4 h between the sample collection and RBC isolation; (iii) phosphate-buffered saline for RBC washing and re-suspendation; (iv) −20 °C for RBC lysis and short-term storage; (v) 50 mmol/L phosphate buffer, pH 7.4, 10 mmol/L DTT as a stabilizing medium for TPN in RBC lysates} demonstrated the suitability of such protocol for a well-defined and reliable routine use in studies on thiopurines TDM.

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Do evacuated blood collection tubes interfere with therapeutic drug monitoring?

Pharmaceutisch Weekblad Scientific Edition ◽

10.1007/bf02074856 ◽

1983 ◽

Vol 5 (6) ◽

pp. 287-290 ◽

Cited By ~ 6

Author(s):

R. Janknegt ◽

J. J. H. M. Lohman ◽

P. M. Hooymans ◽

F. W. H. M. Merkus

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Blood Collection ◽

Blood Collection Tubes

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From therapeutic drug monitoring to total drug monitoring and drug-omics

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-0339 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Michael Vogeser

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Laboratory Medicine ◽

The Other ◽

Therapeutic Drug ◽

Total Drug ◽

The One ◽

The Right ◽

Realistic Goal

AbstractIn view of the role of pharmacotherapy in medicine, on the one hand, and the powerful technical possibilities that are now available on the other hand, therapeutic drug monitoring is a surprisingly neglected area of laboratory medicine. In this viewpoint article, an “omics approach” to pharmacovigilance and drug monitoring is proposed and discussed. A realistic goal for laboratory medicine in the 21st century should indeed be to enable clinicians to check whether the right drug is present in the right patient with an appropriate blood concentration for each compound.

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Diagnose und Monitoring bei chronisch-entzündlicher Darmerkrankung

Therapeutische Umschau ◽

10.1024/0040-5930/a001002 ◽

2018 ◽

Vol 75 (5) ◽

pp. 316-328

Author(s):

Christian Ansprenger ◽

Emanuel Burri

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Morbus Crohn ◽

Therapeutic Drug ◽

Körperliche Untersuchung

Zusammenfassung. Die Diagnose und auch die Überwachung von chronisch entzündlichen Darmerkrankungen ruht auf mehreren Säulen: Anamnese, körperliche Untersuchung, Laborwerte (im Blut und Stuhl), Endoskopie, Histologie und Bildgebung. Die Diagnose kann nicht anhand eines einzelnen Befundes gestellt werden. In den letzten Jahren hat sich das Therapieziel weg von klinischen Endpunkten hin zu endoskopischen und sogar histologischen Endpunkten entwickelt. Für einige dieser neuen Therapieziele existiert allerdings noch keine allgemein gültige Definition. Regelmässige Endoskopien werden von Patienten schlecht toleriert, weshalb Surrogat-Marker wie Calprotectin untersucht wurden und eine gute Korrelation mit der mukosalen Entzündungsaktivität nachgewiesen werden konnte. Entsprechend zeigte sich bei Morbus Crohn eine Algorithmus-basierte Therapiesteuerung – unter anderem basierend auf Calprotectin – einer konventionellen Therapiesteuerung überlegen. Die Überwachung der medikamentösen Therapie («Therapeutic Drug Monitoring» [TDM]) ist ein zweites Standbein des Monitoring von chronisch entzündlichen Darmerkrankungen. Mit zunehmendem Einsatz vor allem der Biologika-Therapien wurden sowohl reaktives TDM (in Patienten mit klinischem Rezidiv) als auch proaktives TDM (in Patienten in Remission / stabiler Erkrankung) untersucht und haben (teilweise) Eingang in aktuelle Richtlinien gefunden. Zukünftige Studien werden die vorgeschlagenen Therapieziele besser definieren und den Nutzen der medikamentösen Therapieüberwachung auf den Krankheitsverlauf weiter untersuchen müssen.

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