Development, validation, and application of a quantitative volumetric absorptive microsampling–based method in finger prick blood by means of LC-HRMS/MS applicable for adherence monitoring of antipsychotics

Abstract

Volumetric absorptive microsampling (VAMS), an emerging microsampling technique, is expected to overcome some disadvantages of dried blood spots such as volume inaccuracy and influence of hematocrit (HT). This study aimed to develop and evaluate a VAMS-based strategy for quantification of 13 frequently prescribed antipsychotics in finger prick blood within the scope of adherence monitoring to complement already-established qualitative urine analysis. The final workflow consisted of VAMS tip hydration and subsequent precipitation. Samples were analyzed by using reversed-phase ultra-high-performance liquid chromatography and Orbitrap mass spectrometry operated in parallel reaction monitoring mode. The analytical procedure was successfully validated based on international recommendations at three different HT values (20%, 40%, 60%) for most of the analytes. Selectivity and within/between-run accuracy and precision were in accordance with the recommendations in most cases. Internal standard–normalized matrix factor met recommended criteria for all analytes at HT 40%. For the HT values of 20% and 60%, only four substances did not meet the criteria. Dilution integrity was given for all substances, except for olanzapine, allowing a quantification over the whole therapeutic range of selected antipsychotics. Long-term stability in VAMS tips was tested and revealed degradation of five antipsychotic drugs after 1 week of storage at 24 °C. A proof of concept of the applicability of the method was obtained by quantification of a selection of the 13 antipsychotic drugs in VAMS tips and matched plasma samples. Results were coherent between matrices. Thus, VAMS was shown to be a promising alternative for adherence monitoring of at least the investigated antipsychotics.

Closing the gap — development of an analytical methodology using volumetric absorptive microsampling of finger prick blood followed by LC-HRMS/MS for adherence monitoring of antihypertensive drugs

“…All other analytes met recommended criteria for accuracy and precision [35]. The advantage of the zero sample compared to the precipitation agent spiked with IS for the dilution of the final extract was shown in previous studies [26,27]. Including the dilution factor, the upper part of the therapeutic range of canrenone and torasemide can be covered.…”

“…S1). VAMS were already used for e.g., screening procedures in different matrices, metabolic studies, therapeutic drug monitoring, and adherence monitoring [23][24][25][26][27].…”

Review of the Preanalytical Errors That Impact Therapeutic Drug Monitoring

“…Haloperidol was stable for 7 days, whereas amisulpride, aripiprazole, clozapine, paliperidone, pipamperone, quetiapine, and risperidone were stable for 2 weeks. 98 Similarly, Velghe et al reported that VAMS specimens were acceptable for the monitoring of 4 antiepileptics, carbamazepine, valproic acid, phenobarbital, and phenytoin. VAMS stored at room temperature, 48C, and 2208C were stable for one month, and when stored at 608C, for 7 days.…”

Advanced Microsamples: Current Applications and Considerations for Mass Spectrometry-Based Metabolic Phenotyping Pipelines

“…Advanced dried sample devices collect samples as a fluid and produce a dried sample either with a polymer tip (volumetric absorptive microsampling, "VAMS"-Neoteryx; Torrance, CA, USA) or carriers akin to DBS cards, such as the hemaPEN (Trajan; Melbourne, VIC, Australia), HemaXis DB10 (DBS System SA; Gland, Switzerland), Capitainer qDBS (quantitative dried blood spot) and B-Vanadate (Capitainer AB; Solna, Sweden), TASSO-M20 (HemoLink; Seattle, WA, USA), and HemaSpot HD and HF (Spot on Sciences; San Francisco, CA, USA) [27,28,36,[66][67][68][69][70][71][72][73]. These technologies improve upon standard DBS cards by providing accurate/volumetric aspiration and thus heamatocrit-independent sample collection over a wide range of microsample sizes (2.74-30 µL).…”