Therapeutic Drug Monitoring In Practice Research Articles

Posaconazole therapeutic drug monitoring in clinical practice and longitudinal analysis of the effect of routine laboratory measurements on posaconazole concentrations.

SummaryPosaconazole is indicated for prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) of posaconazole is used to optimise drug exposure. The aim of this study was to analyse and describe the TDM practices and exposure of posaconazole tablets. Patients who received posaconazole for treatment or prophylaxis of fungal infections were included in the study. The following therapeutic window was defined: if concentration was low (<0.7 mg/L for prophylaxis or < 1.5 mg/L for treatment) or high (>3.75 mg/L), the hospital pharmacist provided the physician with dosage advice, which implementation to patient care was analysed. A longitudinal analysis was performed to analyse if different confounding variables had an effect on posaconazole concentrations. Forty‐seven patients were enrolled resulting in 217 posaconazole trough concentrations. A median of 3 (IQR 1‐7) samples was measured per patient. The median concentration was 1.7 mg/L (IQR 0.8‐2.7) for prophylaxis and 1.76 mg/L (IQR 1.3‐2.3) for treatment. Overall, 78 posaconazole concentrations were out of the therapeutic window. For 45 (54%) of these concentrations, a dosage change was recommended. In the longitudinal analysis, the laboratory markers and patient baseline variables did not have an effect on posaconazole concentrations. Adequate posaconazole exposure was shown in 64% (affected 28 patients) of the measured concentrations. TDM practice of posaconazole can be improved by increasing the implementation rate of dose recommendation by a multidisciplinary antifungal stewardship team.

Survey of Therapeutic Drug Monitoring Practices in Pediatric Health Care Programs across Canada

Therapeutic drug monitoring (TDM) is helpful in situations where a drug has a narrow therapeutic index, a drug dosage does not reliably predict serum concentration, or a serum drug concentration has surrogate value (i.e., is reflective of clinical outcomes). TDM is especially important for the pediatric population, where wide variability in pharmacokinetics and differences in body composition and drug disposition exist. Unfortunately, very little is known about pediatric TDM patterns and the factors that affect the ordering of serum drug measurements. To describe TDM practice for pediatric patients in Canada, to report on the drugs that are monitored and how they are monitored, and to discern factors that influence pediatric TDM patterns. An electronic survey was developed with online survey software and was disseminated to 42 pediatric health care centres in Canada over the period January to March 2016. Of the 42 sites invited to participate in the survey, 20 (48%) responded. All sites reported performing TDM for pediatric patients, and the median number of drugs monitored was 18.5 (range 9-28) per site. The sites differed in terms of TDM practice (e.g., indications for TDM, types of serum drug measurements). Pharmacogenetic testing currently does not play a major role in TDM. Reported barriers to TDM practice include perceived lack of clinical value for certain drugs, limited access to analytical testing, and delayed return of test results. TDM practice is widespread in Canada. To better utilize TDM for clinical practice, future efforts can be aimed toward increasing awareness of the clinical value of TDM and improving the timeliness of access to TDM results.

Therapeutic drug monitoring: using Bayesian methods to evaluate hospital practice

AbstractBackgroundTherapeutic drug monitoring (TDM) is used to improve effectiveness and reduce toxicity of various high‐risk medications. It is guided by drug specific protocols and/or TDM management software.AimThe aim of this study was to evaluate the therapeutic drug monitoring (TDM) of high‐risk drugs, using Bayesian simulation.MethodsPatients prescribed vancomycin, enoxaparin or warfarin and who had plasma concentrations measured for the purposes of TDM were recruited to the study. A Bayesian software package was used to simulate individual patient concentration time curves incorporating patient demographics, dosing data from their course of therapy and all plasma concentrations. The proportion of therapeutic concentrations was determined using the simulated data for each patient and drug. Combined analysis of all patients allowed identification of gaps in TDM at a hospital level. The appropriateness of sampling time and dose adjustments were also investigated.ResultsIn all, 78 patients were recruited who had 279 observed concentrations to allow simulation. Of the 100 observed vancomycin troughs, 66% were sampled incorrectly, as were 34% of 32 observed peak anti‐Xa concentrations (measurement of activity for enoxaparin); all international normalised ratios (INRs) were taken appropriately. Approximately 50% of simulated concentrations were not therapeutic. Most patients administered vancomycin had subtherapeutic concentrations for the first 24–48 h of therapy and most patients treated with enoxaparin had toxic anti‐Xa concentrations within the first 96 h of therapy. INRs were therapeutic only 68% of the time.ConclusionBayesian simulation allowed the identification of gaps in the TDM service and future dose recommendations, including the use of loading doses for vancomycin and dose reductions in extended courses of enoxaparin. TDM practices can now be optimised with the aim of incorporating Bayesian software into clinical practice.

Maximal concentration of intravenous busulfan as a determinant of veno-occlusive disease: a pharmacokinetic-pharmacodynamic analysis in 293 hematopoietic stem cell transplanted children.

Veno-occlusive disease (VOD) is a severe adverse reaction to busulfan-containing regimens used in the preparation of children for hematopoietic stem cell transplantation (HSCT). We conducted a retrospective analysis of data to examine determinants of VOD in children who received IV busulfan for HSCT conditioning. Busulfan PK parameters as well as various indices (maximal concentration-Cmax, area under the concentration-time curve-AUC) were estimated using a validated Bayesian approach. The influence of available PK, demographic, and clinical variables on the incidence of VOD was evaluated by using logistic regression and classification and regression tree (CART) analyses. Among the 293 patients included, the mean age was 6.5 years and the mean actual body weight was 26.3 kg. The incidence of VOD was 25.6%. Busulfan Cmax as well as weight <9 kg or age <3 years were identified as independent predictors of VOD in logistic regression analysis. CART analysis identified busulfan Cmax over the entire regimen as the strongest predictor of VOD. This study suggests that busulfan-associated VOD is in part a concentration-dependent reaction. In addition, the youngest children showed the highest risk of VOD. These findings may have important implications for busulfan dosing and therapeutic drug monitoring practice in HSCT children.

Liquid chromatography-tandem mass spectrometric assay for therapeutic drug monitoring of the EGFR inhibitors afatinib, erlotinib and osimertinib, the ALK inhibitor crizotinib and the VEGFR inhibitor nintedanib in human plasma from non-small cell lung cancer patients

A new method for the quantitative analysis by liquid chromatography-tandem mass spectrometry (LC–MS/MS) of five tyrosine kinase inhibitors (afatinib, crizotinib, osimertinib, erlotinib and nintedanib) used in the treatment of non-small cell lung cancer (NSCLC) was developed and validated in human plasma. Separation was performed on an Accucore® C18 (2.1 × 50 mm; 2.6 μm) column using a gradient elution of water acidified with 0.1% (v/v) formic acid (A) and acetonitrile containing 0.1% (v/v) formic acid (B) at a flow rate of 500 μL/min. The analytes were detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer after positive ionization with heated electrospray interface. After addition of three isotopically labeled internal standards, plasma pretreatment consisted in a simple protein precipitation. This method presented satisfactory results in terms of sensitivity, specificity, precision (intra- and inter-assay coefficient of variation from 2.6% to 10.6%), accuracy (from 96.1% to 108.5%), recovery and matrix effects. The lower limit of quantification and the linearity of these five tyrosine kinases inhibitors are suitable with the expected concentrations in clinical practice. This new bioanalytical method can be used in daily clinical practice for therapeutic drug monitoring of these tyrosine kinase inhibitors in NSCLC patients.

Phenobarbital Dosing and Therapeutic Drug Monitoring in the Neonatal Intensive Care Unit

Phenobarbital is an anticonvulsant used for the treatment of neonatal seizure. Large inter-individual differences in the pharmacokinetics of phenobarbital required therapeutic drug monitoring (TDM). This study aimed to investigate the TDM practices of phenobarbital in the neonatal intensive care unit (NICU) and suggest the appropriate dosing and monitoring guidelines of phenobarbital for critically ill neonates. A single-center, retrospective chart review included NICU patients with a TDM consult of phenobarbital by a pharmacist and at least 1 serum concentration obtained. A total 79 drug concentration values for 28 patients were included in the analysis. The percentage of phenobarbital concentrations within the therapeutic range (15-40 mg/L) was 65.8%. Sub-therapeutic levels (< 15 mg/L) were observed in 25 instances (31.6%). The percentage of concentrations within therapeutic range was significantly lower in preterm infants (52.9%) than in term infants (75.6%, p=0.024). Oral administration resulted in a significantly higher percentage of sub-therapeutic concentrations than intravenous administration (57.7% versus 18.9%, p=0.002). Patients with oral and intravenous administration received maintenance doses 3.5±1.1 and 3.9±1.1 mg/kg/day, respectively (p=0.114). The percentage of cases requiring dosage adjustment by a pharmacist was 41.8%. The rate of acceptance of pharmacist`s recommendations by physicians was 87.3%. For effective and safe treatment of phenobarbital in NICU patients, close monitoring is essential for preterm infants and the development of optimal dosing guideline for oral administration is required.

Current Practice of Therapeutic Drug Monitoring of Biopharmaceuticals in Psoriasis Patients.

The high prevalence of psoriasis and the high spending on pharmaceuticals motivate a more evidence-based and cost-effective usage of biopharmaceuticals. A growing body of evidence exists that the implementation of therapeutic drug monitoring for biopharmaceuticals in psoriasis patients optimizes patient management and clinical outcome and enhances their efficacy. Therefore, the aim of this review was to give an overview of the literature on therapeutic drug monitoring of biopharmaceuticals in the treatment of psoriasis and to provide the useful information to dermatologists to improve health care in psoriasis patients.

Current Practice for Therapeutic Drug Monitoring of Biopharmaceuticals in Rheumatoid Arthritis.

The treatment of rheumatoid arthritis (RA) has largely improved in the biopharmaceutical era. These compounds, primarily tumor necrosis factor (TNF) inhibitors, are effective, but some patients may show poor response, sometimes because of the presence of antidrug antibodies (ADAs). In some instances, clinicians may increase or taper the dose depending on the clinical response. Besides the current clinical-based practice, a tailored strategy based on drug monitoring has emerged as a way to improve the use of these drugs. However, the relevance of this therapeutic drug monitoring (TDM) of biopharmaceuticals in RA is still unknown. In this literature review, we examine the most relevant articles dealing with the concentration-response relationship, ADA detection and pharmacokinetics in RA patients receiving biopharmaceuticals. A concentration-response relationship was clearly established for TNF inhibitors. Moreover, ADA positivity was associated with low drug concentrations, poor clinical outcome, and reduced drug survival for TNF-inhibitor monoclonal antibodies. Concomitant use of disease-modifying antirheumatic drugs, especially methotrexate, is associated with good clinical outcome, increased drug concentrations, and reduced immunogenicity. Strategies based on TDM of TNF inhibitors seem promising for RA, but randomized controlled trials are required to support this. A concentration-response relationship may exist with tocilizumab, and immunogenicity seems rare. Finally, the relevance of TDM for RA patients receiving rituximab and abatacept remains unclear.

Current Practice for Therapeutic Drug Monitoring of Biopharmaceuticals in Inflammatory Bowel Disease.

Since the late 90s, biopharmaceuticals targeting tumor necrosis factor alpha have revolutionized the treatment of moderately to severely active inflammatory bowel disease. The robust efficacy witnessed in many patients stands in stark contrast with the observation of a proportion of patients who fail to respond or who lose response over time. Therapeutic drug monitoring has been proposed as a means to understand and respond to the variability in clinical response and remission. Various treatment algorithms have been proposed, but optimal use of these measurements in daily practice awaits additional prospective validation trials. This review provides an updated overview on the subject of therapeutic drug monitoring of biopharmaceuticals for the management of inflammatory bowel disease and how we could implement its concepts in a changing landscape.

Current Practice for Therapeutic Drug Monitoring of Biopharmaceuticals in Spondyloarthritis

Treatment of spondyloarthritis (SpA) has greatly improved in the biopharmaceutical era. These compounds, primarily tumor necrosis factor inhibitors, are effective, but some patients may show poor response, sometimes due to the presence of antidrug antibodies (ADAs). In some instances, clinicians may increase or taper the dose, depending on the clinical response. Besides the current clinical practice, a tailored strategy based on drug monitoring is emerging as a way to improve the use of these drugs. However, the relevance of this therapeutic drug monitoring of biopharmaceuticals for SpA is still unknown. In this literature review, we examined the most relevant articles dealing with the concentration-response relation, ADA detection, and pharmacokinetics in SpA treated with biopharmaceuticals. ADAs were associated with low or undetectable concentration of monoclonal antibodies. The relation between drug concentration and clinical response in SpA is debated, some studies showing an association and others not. Therefore, therapeutic drug monitoring of biopharmaceuticals for SpA requires a better understanding of the association among the pharmacokinetics, pharmacodynamics, and immunogenicity of these drugs.

Overview of systematic reviews of therapeutic ranges: methodologies and recommendations for practice

BackgroundMany medicines are dosed to achieve a particular therapeutic range, and monitored using therapeutic drug monitoring (TDM). The evidence base for a therapeutic range can be evaluated using systematic reviews, to ensure it continues to reflect current indications, doses, routes and formulations, as well as updated adverse effect data. There is no consensus on the optimal methodology for systematic reviews of therapeutic ranges.MethodsAn overview of systematic reviews of therapeutic ranges was undertaken. The following databases were used: Cochrane Database of Systematic Reviews (CDSR), Database of s and Reviews of Effects (DARE) and MEDLINE. The published methodologies used when systematically reviewing the therapeutic range of a drug were analyzed. Step by step recommendations to optimize such systematic reviews are proposed.ResultsTen systematic reviews that investigated the correlation between serum concentrations and clinical outcomes encompassing a variety of medicines and indications were assessed. There were significant variations in the methodologies used (including the search terms used, data extraction methods, assessment of bias, and statistical analyses undertaken). Therapeutic ranges should be population and indication specific and based on clinically relevant outcomes. Recommendations for future systematic reviews based on these findings have been developed.ConclusionEvidence based therapeutic ranges have the potential to improve TDM practice. Current systematic reviews investigating therapeutic ranges have highly variable methodologies and there is no consensus of best practice when undertaking systematic reviews in this field. These recommendations meet a need not addressed by standard protocols.

Therapeutic drug monitoring in the past 40 years of the Journal of Antimicrobial Chemotherapy.

Since the Journal of Antimicrobial Chemotherapy was first published in 1975, papers addressing therapeutic drug monitoring (TDM) have been a regular feature. Initially they focused on laboratory aspects of drug concentration measurement then they changed more to the application of TDM in a clinical setting. Over its history, the Journal has provided its readership with the latest technological and scientific advances in TDM and has helped to drive changes in TDM that have directly impacted on patient care. These have varied from improvement in the quality of antimicrobial measurements through better identification of dosage regimens and TDM targets that help predict outcome and adverse events. Despite these advances in our understanding of the science and practice of TDM, there remain many areas of uncertainty. As we move into the next 40 years, it is clear that the Journal will continue to provide the readership with the latest science and opinion in this important area.

Therapeutic Index Estimation of Antiepileptic Drugs: A Systematic Literature Review Approach.

Our study aimed to determine whether data obtained from the medical literature can be used to estimate the therapeutic index of 5 antiepileptic drugs (AEDs): carbamazepine, lamotrigine, phenobarbital, phenytoin, and valproate. We performed a literature search using PubMed and EMBASE to collect published safety, efficacy, and therapeutic monitoring data for 5 AEDs and extracted all relevant information into a drug- and study-specific drug database. For each AED, we summarized (1) type, severity, and incidence of toxicity-related adverse events and toxicity-associated range of drug doses or concentrations; (2) effective versus toxic concentration and dose (therapeutic range); and (3) therapeutic drug monitoring practices. We defined therapeutic index as the ratio of the minimum toxic concentration to the minimum effective concentration. We reviewed a total of 810 full-text articles and extracted data from 163. The literature suggests that the therapeutic index of phenytoin is 2. The therapeutic indices of phenobarbital and valproate exceed 2. There were insufficient data to precisely quantify the therapeutic indices of carbamazepine and lamotrigine. For some drugs, this approach offers a low-cost method of therapeutic index estimation. Our results can serve as preliminary data for future trials and as guidance for US Food and Drug Administration decision making regarding narrow therapeutic index classification.

Voriconazole Therapeutic Drug Monitoring Practices in Intensive Care

Routine therapeutic drug monitoring of voriconazole seems to be beneficial. This study investigated the therapeutic drug monitoring practices in intensive care to derive possible recommendations for improvement. A retrospective chart review was performed for patients aged ≥18 years who started treatment with voriconazole, which lasted for at least 3 days while being admitted to an intensive care unit to assess possible differences between the patients with and without voriconazole trough concentrations measured. In 64 (76%) of the 84 patients, voriconazole trough concentrations were measured. The groups differed significantly with respect to the duration of voriconazole treatment and intensive care unit admission. Time of sampling was very early and therefore inappropriate for 49% of the first measured voriconazole trough concentrations and in 48% of the subsequent measured concentrations. Of the 349 trough concentrations measured, 129 (37%) were outside the therapeutic window. In 11% of these cases, no recommendation was provided without identifiable reason. In addition, 27% of recommended dose adjustments were not implemented, probably because the advice was not suited for the specific clinical situation. The performance of voriconazole therapeutic drug monitoring can still be improved although voriconazole concentrations were monitored in most patients. A multidisciplinary approach-for instance by means of antifungal stewardship-will probably be able to overcome problems encountered such as timing of sampling, incompleteness of data in clinical context, and lack of implementation of recommendations.

Consensus Guideline Based Therapeutic Drug Monitoring (TDM) in Psychiatry and Neurology.

Therapeutic drug monitoring (TDM) is a valuable tool for tailoring the dosage of the prescribed medication(s) to the individual pharmacokinetic characteristics of a patient. In psychiatry and neurology, however, proven evidence that TDM should be used for treatment with the multiple neuropsychiatric medications is restricted to few compounds. Well-designed clinical trials on medical and economic benefits of TDM are rare. The use of TDM is limited in most countries to few antiepileptics, especially carbamazepine, phenobarbital and phenytoin, some mood stabilizers, especially lithium and valproic acid, some antidepressants, especially tricyclic antidepressants and some antipsychotics, primarily clozapine because these drugs have a narrow therapeutic index. On the other hand, specific indications and distinct problems can make TDM most useful for individualized pharmacotherapy with almost any neuropsychiatric drug. Potential benefits of TDM can, however, only be reaped if the method is adequately integrated into the clinical treatment process. The TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued consensus guidelines for the best practice of TDM in psychiatry and neurology. A first version was published in 2004. These guidelines were extended in 2011 and are actually updated (see: www.agnp.de). Exemplified by single cases it is shown here how to use TDM consensus guidelines for problem solving in psychiatry and neurology. Studies on depressed patients give evidence for tricyclic antidepressants, venlafaxine and citalopram that TDM could become a standard of care in psychiatry and neurology. There is potential to accelerate improvement. Reducing phases of suffering will not only have medical benefits for the patients but also an impact on costs for the health system which needs to be clarified by controlled studies.

The ANTIBIOPERF study: a nationwide cross-sectional survey about practices for β-lactam administration and therapeutic drug monitoring among critically ill patients in France

Our objective was to assess current practices about the administration (intermittent, extended, or continuous infusions) and therapeutic drug monitoring (TDM) of β-lactam antibiotics and vancomycin in France. We conducted a nationwide cross-sectional survey in May–August 2015, using an online questionnaire, sent as an e-mail link to infectious disease specialists and intensive care specialists through national mailing lists. We used clinical vignettes of critically ill patients to assess physicians’ practices about administration and TDM practices for amoxicillin, cloxacillin, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, meropenem and vancomycin. In all, 507 physicians participated (507/1200, response rate 42%). TDM was rarely available for β-lactams (from 16.5% (81/490) for cloxacillin to 30% (145/490) for ceftazidime), whereas vancomycin TDM was available in 97% (477/490) of the cases. In the clinical vignettes, ceftazidime and piperacillin/tazobactam were the β-lactams administered most frequently by extended or continuous infusions (76% (336/440) and 57% (252/444), respectively). Gaps in knowledge about the duration of stability of intravenous β-lactams were common (correct answers ranged from 8% (35/432) for cloxacillin to 33% (146/438) for ceftazidime). Most physicians (77%, 339/442) were convinced of the value of extended or continuous infusions for β-lactams in critically ill patients, but 48% (211/442) did not have access to practical guidelines. Our survey found that most infectious disease and intensive care specialists are favourable to optimized administration of β-lactams in critically ill patients. But the lack of guidelines and limited TDM availability for β-lactams in hospitals are potential barriers to its implementation.

A modeling tool for the personalization of pharmacokinetic predictions

Abstract A method to apply pharmacokinetic models to assist physicians in therapeutic drug monitoring is proposed. The practice of therapeutic drug monitoring is required for drugs characterized by a narrow therapeutic index, which consequently present toxicity concerns. The proposed method employs a physiologically based pharmacokinetic (PBPK) model to determine an initial assessment of the pharmacokinetics (PK) of a specific patient. To further increase the precision of this prediction, the method uses two experimental datasets: (i) the PK data from a group of reference subjects, and (ii) limited drug blood concentration measures of the specific patient under study. By combining the available information, it is possible to assess the precision of the initial model prediction and determine a correction factor to improve it. The resulting patient-specific PBPK model produces encouraging results as there is a concrete reduction in prediction errors of the individualized PK with respect to experimental data.

Quantification of selected antidepressants and antipsychotics in clinical samples using chromatographic methods combined with mass spectrometry: A review (2006-2015).

Psychiatric disorders contribute significantly to worldwide morbidity and mortality. In the case of depression and schizophrenia, effective drug therapy is available but 30-50% of patients do not respond sufficiently to the initial treatment regimen. Apart from the development of new molecules, it is desirable to optimize treatment outcomes with agents that are currently available. Therapeutic drug monitoring (TDM) is a suitable and widely accepted approach for improving the efficacy and safety of these drugs. A review of the relevant literature published between 2006 and January 2015. This review describes major advances and drawbacks in the field of chromatography coupled with single or tandem mass spectrometry (LC-MS, LC-MS/MS and GC/MS) of selected antidepressants (agomelatine, vilazodone) and antipsychotics (iloperidone, asenapine, amisulpride, aripiprazole, melperone, zotepine, ziprasidone). The high specificity in combination with high sensitivity makes these techniques an attractive complementary method to traditional procedures used in routine practice for TDM.

Optimizing dosing of antibiotics in critically ill patients.

Recent studies suggest that contemporary antibiotic dosing is unlikely to achieve best outcomes for critically ill patients because of extensive pharmacokinetic variability and altered pharmacodynamics. Dose adaptation is considered quite challenging because of unpredictable dose-exposure relationships. Consequently, individualization of antibiotic dosing has been advocated. Herein, we describe recent developments in the optimization of antibiotic dosing in the critically ill. Conventional doses of many antibiotics frequently result in sub or supratherapeutic exposures in the critically ill. Clinical studies continue to illustrate that dose-exposure relationships are highly variable in severely ill patients. Dose optimization based on pharmacokinetic/pharmacodynamic principles can effectively improve antibiotic exposure. Therapeutic drug monitoring (TDM) with adaptive feedback is likely to be the most robust approach to optimize dosing for individual patients. This more accurate approach to dosing is made possible with the user-friendly dosing software that is emerging. The scope of TDM is broadening from the traditional focus on prevention of toxicity, to include optimization of antibiotic exposure thereby improving patient outcomes. However, the evidence relating TDM practice with improved clinical outcome remains limited. Well designed, multicentre, randomized controlled studies are warranted.

Fast simultaneous LC/MS/MS determination of 10 active compounds in human serum for therapeutic drug monitoring in psychiatric medication.

A UPLC/MS/MS method with simple protein precipitation has been validated for the fast simultaneous analysis of agomelatine, asenapine, amisulpride, iloperidone, zotepine, melperone, ziprasidone, vilazodone, aripiprazole and its metabolite dehydro-aripiprazole in human serum. Alprenolol was applied as an internal standard. A BEH C18 (2.1 × 50 mm, 1.7 µm) column provided chromatographic separation of analytes using a binary mobile phase gradient (A, 2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v; B, 2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v). Mass spectrometric detection was performed in the positive electrospray ionization mode and ion suppression owing to matrix effects was evaluated. The validation criteria were determined: linearity, precision, accuracy, recovery, limit of detection, limit of quantification, reproducibility and matrix effect. The concentration range was as follows: 0.25-1000 ng/mL for agomelatine; 0.25-100 ng/mL for asenapine and iloperidone; 2.5-1000 ng/mL for amisulpride, aripiprazole, vilazodone and zotepine; 2.3-924.6 ng/mL for dehydroaripiprazole; 2.2-878.4 ng/mL for melperone; and 2.2-883.5 ng/mL for ziprasidone. Limits of quantitation below a therapeutic reference range were achieved for all analytes. Intra-run precision of 0.4-5.5 %, inter-run precision of 0.6-8.2% and overall recovery of 87.9-114.1% were obtained. The validated method was successfully implemented into routine practice for therapeutic drug monitoring in our hospital.