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

Abstract

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

Microsampling Devices for Routine Therapeutic Drug Monitoring—Are We There Yet?

“…Moreover, as most target therapeutic concentration ranges have been derived in plasma or serum, a dried plasma spot (DPS) sample should require little or no changes to the established reference ranges, rendering the interpretation of results more straightforward. However, although several methods have revealed the potential of DPS for measuring drugs for TDM purposes, 50,51 the sampling strategy still requires a clinical setting as the sample of plasma/ serum has to be obtained from a sample of whole blood. Hence, devices are required to generate a fixed volume of plasma, preferably onto a dried format, from a sample of capillary blood.…”

Fast and Simple Liquid Chromatography-Isotope Dilution Tandem Mass Spectrometry Method for Therapeutic Drug Monitoring of Dalbavancin in Long-Term Treatment of Subacute and/or Chronic Infections

“…The use of plasma microsampling techniques in TDM of long-term treatment regimens may have some practical advantages compared to conventional venipuncture methods [ 9 ]. Microsampling enables the reduction of stress and pain related to venipuncture procedures and may be particularly advisable in fragile populations [ 10 , 11 ]. Blood microsamples may be collected onto specialty paper(s) [ 11 ], polymeric tips or capillaries [ 9 ] and even directly collected onto dried plasma spots (DPS) [ 12 ].…”

“…Microsampling enables the reduction of stress and pain related to venipuncture procedures and may be particularly advisable in fragile populations [ 10 , 11 ]. Blood microsamples may be collected onto specialty paper(s) [ 11 ], polymeric tips or capillaries [ 9 ] and even directly collected onto dried plasma spots (DPS) [ 12 ]. Blood droplets can also be collected in small, dedicated vials, and plasma can be obtained by centrifugation in the laboratory.…”

Dried plasma spot–based liquid chromatography–tandem mass spectrometry for the quantification of methotrexate in human plasma and its application in therapeutic drug monitoring

“…Recently, dried blood spot (DBS) and dried plasma spot (DPS) sampling have become popular alternative microsampling strategies in the field of TDM. Compared with traditional sampling methods, both of these microsampling methods have the advantages of a less invasive sampling technique, smaller sample size, selfsample collection even at patients' homes or remote locations, convenient storage, room temperature (RT) transportation, and reduced infectious disease transmission risk [24][25][26][27][28][29][30]. These samples are easier to collect than serum or plasma samples because they do not require venipuncture and centrifugation and are easier to preserve because they do not need refrigeration.…”