LC–MS/MS method for the simultaneous analysis of seven antimalarials and two active metabolites in dried blood spots for applications in field trials: Analytical and clinical validation

Gallay, Joanna; Prod’hom, Sylvain; Mercier, Thomas; Bardinet, Carine; Spaggiari, Dany; Pothin, Emilie; Buclin, Thierry; Genton, Blaise; Décosterd, Laurent A.

doi:10.1016/j.jpba.2018.01.017

Cited by 36 publications

(20 citation statements)

References 66 publications

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“…Nevertheless, there are some good reasons for hope regarding the future of TDM. Analytical methods continue to progress toward better simplicity, operability, and automation, enabling, e.g., the use of alternative matrices such as saliva, interstitial fluid or dried blood spots facilitating sample collection (Gallay et al, 2018). In another direction, point-of-care TDM methods are currently being developed (Sanavio and Krol, 2015), using innovative analytical methods (Tenaglia et al, 2018).…”

Section: Discussion: Current Hurdles and Prospect For Tdmmentioning

confidence: 99%

The Steps to Therapeutic Drug Monitoring: A Structured Approach Illustrated With Imatinib

et al. 2020

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Pharmacometric methods have hugely benefited from progress in analytical and computer sciences during the past decades, and play nowadays a central role in the clinical development of new medicinal drugs. It is time that these methods translate into patient care through therapeutic drug monitoring (TDM), due to become a mainstay of precision medicine no less than genomic approaches to control variability in drug response and improve the efficacy and safety of treatments. In this review, we make the case for structuring TDM development along five generic questions: 1) Is the concerned drug a candidate to TDM? 2) What is the normal range for the drug's concentration? 3) What is the therapeutic target for the drug's concentration? 4) How to adjust the dosage of the drug to drive concentrations close to target? 5) Does evidence support the usefulness of TDM for this drug? We exemplify this approach through an overview of our development of the TDM of imatinib, the very first targeted anticancer agent. We express our position that a similar story shall apply to other drugs in this class, as well as to a wide range of treatments critical for the control of various life-threatening conditions. Despite hurdles that still jeopardize progress in TDM, there is no doubt that upcoming technological advances will shape and foster many innovative therapeutic monitoring methods.

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Section: Discussion: Current Hurdles and Prospect For Tdmmentioning

confidence: 99%

The Steps to Therapeutic Drug Monitoring: A Structured Approach Illustrated With Imatinib

et al. 2020

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“…Daughter ions were selected by studying MS/MS spectra obtained by summing‐up collision‐induced dissociation spectra at various collision energies, in the range from 5 to 100 eV. In addition to these experimental observations, data available in the literature were also used as a guide to transition selection [12‐24].…”

Section: Resultsmentioning

confidence: 99%

“…Classically, liquid whole blood, serum or plasma samples (LPs) (obtained from brachial venipuncture) are employed in the TDM of antipsychotics and concentration reference ranges are available for the interpretation of TDM results [2]. Recently, dried blood (DB), serum, or dried plasma (DP) spot samples have been shown as convenient alternatives to conventional liquid samples for drug measurement [15‐31]. They are easier to collect (even by a self‐directed simple finger pricking), easier to conserve, and to ship abroad because they do not require refrigeration, since analyte degradation is minimized in the absence of water [16].…”

Section: Introductionmentioning

confidence: 99%

Multiplexed therapeutic drug monitoring of antipsychotics in dried plasma spots by LC‐MS/MS

Ruggiero¹,

Ramirez²,

Ramazzotti³

et al. 2020

J of Separation Science

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In this work, a convenient method for the therapeutic monitoring of seven common antipsychotic drugs in "dried plasma spot" samples has been developed. It is based on the liquid chromatography tandem mass spectrometry technique, operating in multiple reaction monitoring mode, and a straightforward procedure for the simultaneous extraction of all antipsychotics in a single step, with high extraction yield. The method was fully validated with proper accuracy, precision, selectivity and sensitivity, for all the drugs. Limits of quantification were 0.12, 1.09, 1.46, 1.47, 5.70, 1.32, 1.33 µg/L for haloperidol, aripiprazole, olanzapine, quetiapine, clozapine, risperidone, and paliperidone, respectively. Accuracy, intra-and interday precision values were <10% for all drugs at all concentration levels examined. The method was tested in the analysis of 30 plasma samples from real patients for each drug. The proposed analytical approach, by combining practical and logistical advantages of microsampling with liquid chromatography tandem mass spectrometry analytical performance, could offer an ideal strategy for accurate and timely therapeutic drug monitoring of antipsychotic drugs in most clinical settings, even in remote centers and/or in out-patient settings, bringing so many potential improvements in psychiatric patient care. K E Y W O R D Santipsychotic drugs, dried plasma spots, liquid chromatography-mass spectrometry, therapeutic drug monitoring 1440

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“…The analytical method achieved good performances in terms of trueness (-12.1 to +11.1%) and precision (1.4 to 15.0%). All analytes were stable in DBS kept for 24h at room temperature and at 37°C [ 33 , 34 ]. They were also found to be stable when mimicking the study storage and transportation conditions (unpublished data).…”

Section: Methodsmentioning

confidence: 99%

“…Individuals were considered having an antimalarial in the blood if the concentrations measured in their corresponding DBS sample were equal or higher than the lower limit of quantification (LOQ) [ 34 ]. Age was categorized as presented in Tables 1 and 2 , based on the age distribution of the sampled population.…”

Section: Methodsmentioning

confidence: 99%

Predictors of residual antimalarial drugs in the blood in community surveys in Tanzania

et al. 2018

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BackgroundUnderstanding pattern of antimalarials use at large scale helps ensuring appropriate use of treatments and preventing the spread of resistant parasites. We estimated the proportion of individuals in community surveys with residual antimalarials in their blood and identified the factors associated with the presence of the most commonly detected drugs, lumefantrine and/or desbutyl-lumefantrine (LF/DLF) or sulfadoxine-pyrimethamine (SP).MethodsA cross-sectional survey was conducted in 2015 in three regions of Tanzania with different levels of malaria endemicity. Interviews were conducted and blood samples collected through household surveys for further antimalarial measurements using liquid chromatography coupled to tandem mass spectrometry. In addition, diagnosis and treatment availability was investigated through outlet surveys. Multilevel mixed effects logistic regression models were used to estimate odds ratios for having LF/DLF or SP in the blood.ResultsAmongst 6391 participants, 12.4% (792/6391) had LF/DLF and 8.0% (510/6391) SP in the blood. Factors associated with higher odds of detecting LF/DLF in the blood included fever in the previous two weeks (OR = 2.6, p<0.001), living in districts of higher malaria prevalence (OR = 1.5, p<0.001) and living in a ward in which all visited drug stores had artemisinin-based combination therapies in stocks (OR = 2.7, p = 0.020). Participants in older age groups were less likely to have LF/DLF in the blood (OR = 0.9, p<0.001). Factors associated with higher odds of having SP in the blood included being pregnant (OR = 4.6, p<0.001), living in Mwanza (OR = 3.9, p<0.001 compared to Mbeya), fever in the previous two weeks (OR = 1.7, p<0.001) and belonging to older age groups (OR = 1.2, p<0.001).ConclusionThe most significant predictors identified were expected. History of fever in the past two weeks and young age were significant predictors of LF/DLF in the blood, which is encouraging. Antimalarial drug pressure was high and hence the use of recommended first-line drugs in combination with malaria Rapid Diagnostics Tests should be promoted to ensure appropriate treatment.

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LC–MS/MS method for the simultaneous analysis of seven antimalarials and two active metabolites in dried blood spots for applications in field trials: Analytical and clinical validation

Cited by 36 publications

References 66 publications

The Steps to Therapeutic Drug Monitoring: A Structured Approach Illustrated With Imatinib

The Steps to Therapeutic Drug Monitoring: A Structured Approach Illustrated With Imatinib

Multiplexed therapeutic drug monitoring of antipsychotics in dried plasma spots by LC‐MS/MS

Predictors of residual antimalarial drugs in the blood in community surveys in Tanzania

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