Validation and Clinical Application of a Volumetric Absorptive Microsampling Method for 14 Psychiatric Drugs

Abstract

Aim: Volumetric absorptive microsampling offers a hematocrit insensitive way for microsampling. The aim of this study was to develop a method for routine healthcare for 14 antidepressants, antipsychotics and their active metabolites on a single-quadrupole HPLC–MS. A clinical validation study to determine conversion factors from capillary blood to plasma concentration was conducted afterward. Results: The method was validated according to current guidelines except for one substance. Five substances were measured in 49 patient samples and conversion factors could be derived with Passing–Bablok and Bland–Altman analysis. Conclusion: A reliable extraction and analysis method for commonly used antidepressants and antipsychotics was developed and validated. The method with the obtained conversion factors can now be used in routine healthcare.

Graphical abstract

The tip of the volumetric absorptive microsampling device is removed and put into a small reaction vessel. A prewetting step with 50 μl water for 15 min is followed by adding 250 μl of methanol with internal standard. The sample is then shaken for 10 min, sonicated for 15 min and shaken again for additional 10 min. After centrifugation, 130 μl of the supernatant are injected into the HPLC–MS.

Keywords:

• antidepressants
• antipsychotics
• clinical validation
• dried blood spots
• LC–MS
• Mitra
• therapeutic drug monitoring
• validation
• VAMS
• volumetric absorptive microsampling

Author contributions

M Stern: sample collection, laboratory work, evaluation of the results and writing of the manuscript; Melanie Giebels: patient recruitment, study doctor; T Fey: patient recruitment, responsible study doctor; M Lübking: patient recruitment; J Alferink: patient recruitment and collaborated study doctor; G Hempel: supervision of the project, writing of the manuscript.

Acknowledgements

The authors give many thanks to the nurses and other co-workers in both hospitals for the cooperation during the clinical validation study. The authors also give special thanks to C Rimmler for proofreading the manuscript and for giving recommendations. The authors also give many thanks to G Wuerthwein for the statistical help.

Financial & competing interests disclosure

Parts of this project were funded by the Apothekerstiftung Westfalen-Lippe as part of a project to transfer TDM as pharmaceutical service into public pharmacies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, written informed consent has been obtained from the participants involved.

Data sharing statement

Original data with pseudonymous patient names is available from the authors on request.

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2144/000112170