Drug Therapy Research Articles

Haemolytic Anaemia-Related Pulmonary Hypertension

Haemolytic anaemia represents a risk factor for the development of pulmonary hypertension (PH), currently classified as World Health Organization group 5 PH, and data regarding appropriate therapeutic strategy are limited. A total of 28 patients, 85.7% with thalassaemia and 14.3% with sickle cell disease, with a diagnosis of PH confirmed by right heart catheterization were included in the study. The patients were divided into three groups according to the PH haemodynamic definition and overall diagnostic approach: 42.9% had precapillary PH (pulmonary arterial hypertension—PAH group), 25% had post-capillary PH, and 32.1% had chronic thromboembolic PH (CTEPH) (29% of b-thalassemia and 50% of SCD patients). The therapeutic approach in each group and its impact on the outcome and haemodynamics were recorded. PAH-specific drug therapy received 82.1% of patients, and balloon pulmonary angioplasty (BPA) was performed in six patients with CTEPH. There were statistically significant differences in baseline mPAP and PVR values between the CTEPH-haemolytic anaemia group and other groups. PAH-specific drug therapy resulted in haemodynamic improvement for the PAH group. Patients who underwent BPA had improved pulmonary haemodynamics. The median survival time was 162 months, and the survival rate was 1 year—100%; 2, 3, 4, 5, and 6 years—96%; 9 years—90%; and 13 years—78%. In patients with haemolytic anaemia, the wide spectrum of induced PH highlighted the importance of a correct predominant diagnosis. BPA in CTEPH patients and specific-PAH drug therapy for PAH patients represent potential therapeutic strategies; however, the management should be offered in expert PH centres under individualized approaches for patients.

The Treatment of Hepatocellular Carcinoma with Major Vascular Invasion

Vascular invasion of hepatocellular carcinoma involves tumor plugs in the main trunk of the portal vein, bile ducts, and veins, and it indicates poor prognosis. It is often associated with portal hypertension, which requires evaluation and management. Treatment includes hepatic resection, systemic pharmacotherapy, hepatic arterial infusion chemotherapy, and radiation therapy. Recurrence rates post-hepatic resection are high, and systemic drug therapy often has limited therapeutic potential in patients with a poor hepatic reserve. Single therapies are generally inadequate, necessitating combining multiple therapies with adjuvant and systemic pharmacotherapy before and after hepatectomy. This narrative review will provide an overview of the treatment of hepatocellular carcinoma with vascular invasion.

Pharmacogenomics: A Genetic Approach to Drug Development and Therapy

The majority of the well-known pharmacogenomics research used in the medical sciences contributes to our understanding of medication interactions. It has a significant impact on treatment and drug development. The broad use of pharmacogenomics is required for the progress of therapy. The main focus is on how genes and an intricate gene system affect the body’s reaction to medications. Novel biomarkers that help identify a patient group that is more or less likely to respond to a certain medication have been discovered as a result of recent developments in the field of clinical therapeutics. It aims to improve customized therapy by giving the appropriate drug at the right dose at the right time and making sure that the right prescriptions are issued. A combination of genetic, environmental, and patient variables that impact the pharmacokinetics and/or pharmacodynamics of medications results in interindividual variance in drug response. Drug development, illness susceptibility, and treatment efficacy are all impacted by pharmacogenomics. The purpose of this work is to give a review that might serve as a foundation for the creation of new pharmacogenomics applications, techniques, or strategies.

Factors Determining Quality of Drug Information by Hospital Pharmacies—Results from Five-Year Annual Quality Assessment

Drug information (DI) provided by hospital pharmacies aims to promote rational and safe drug therapy. While quality assessment for this task is recommended, more knowledge on the factors determining the quality is needed. We aimed to evaluate the impacts of different factors on the quality of DI provided by hospital pharmacies to healthcare professionals. Retrospectively, answers on fictitious enquiries about annual DI tests for German hospital pharmacies over five years were evaluated for content-related and structural requirements. Multivariate analysis was performed for the impact of the enquiry complexity, DI organization (specialized DI center; pharmacist responsible per day; DI on top of other routine tasks), and quality measures (second look; experience of answering pharmacist in DI/on ward; use of documentation database). In 2017–2021, 45, 71, 79, 118, and 122 hospital pharmacies participated. The enquiry complexity had a statistically significant impact on the content-related quality, with poor results for a higher complexity (years 2018/2021, OR 0.25/0.04, p < 0.01). The DI centers achieved better results regarding content-related quality than for a pharmacist responsible per day (OR 0.76/p = 0.65) or DI on top of routine tasks (OR 0.35/p = 0.02). The DI centers scored better in structural quality. The second look showed an overall trend of a better content-related and structural quality. In conclusion, specialized DI centers and second looks are recommended as quality-improving measures. Training for answering complex enquiries should be intensified.

Acne treatment: research progress and new perspectives

Acne is a chronic inflammatory skin disease that primarily affects adolescents and is attributed to various factors, including hormonal changes, genetic predisposition, and environmental influences. It typically manifests in areas rich in sebaceous glands such as the face, chest, and back. Symptoms of acne can range from mild to severe and may present as pimples, pustules, nodules, cysts, and scarring. The appearance of acne can significantly impact both the physical and mental well-being of patients, potentially leading to feelings of anxiety, depression, and social withdrawal. The pathogenesis of acne is multifaceted involving genetic predisposition as well as environmental factors such as hormonal imbalances, inflammation, abnormal follicular sebaceous unit keratinization, proliferation of follicular microorganisms like Propionibacterium acnes, increased sebum production, and dietary influences. Traditional treatment methods for acne include topical drug therapy, oral drug therapy, photoelectric therapy, and chemical peeling. With ongoing research into the pathogenesis of acne, treatment methods are rapidly evolving with novel antibiotics, probiotics, biological agents, topical anti-androgen drugs, topical vitamin A acid metabolism blockers, antimicrobial peptides, immunotherapy, micro-needling, and micro-needling patches. This article aims to provide a comprehensive review of recent advancements in acne treatment.

Integrated management of multiple drugs for cardiovascular disease in older adults

Background: Older people have a high frequency of use of medical institutions due to their multiple comorbidities, which increases the frequency of drug-related problems or adverse drug reactions, such as duplicate prescriptions and inappropriate drug use. Polypharmacy in older people increases the risk of side effects and drug-drug interactions, thereby affecting health outcomes and quality of life. Because most elderly person with cardiovascular disease are already taking multiple drugs, the risk is inevitably high. Therefore, there is a need to develop strategies to mitigate the adverse effects of multidrug therapy in older adults with cardiovascular diseases.Current Concepts: We reviewed the latest relevant guidelines and literature in order to provide practical considerations for appropriate prescriptions for older people with cardiovascular disease, balancing unnecessary or harmful drugs with proven long-term benefits.Discussion and Conclusion: Continuous dialogue between healthcare providers and patients allows the close monitoring of drug efficacy and the prevention of adverse events. Drug therapy requires individualization as treatment goals vary with advancing age.

Economic evaluations of therapeutic drug monitoring interventions in acute hospital-based settings: A systematic review.

Therapeutic drug monitoring (TDM) aims to optimize drug therapy. As demand on health resources increases, and the technology underpinning TDM becomes more sophisticated, the economic benefits of TDM in hospitals is unclear. The aim of this systematic review was to summarize the economic evidence that could be used to support investment in TDM in hospital settings. In so doing, we sought to provide guidance for future economic evaluations. Medline, Embase, CENTRAL, Econlit and NHS Economic Evaluation databases were searched (inception to December 2022) for economic evaluations of hospital-based TDM. Two authors reviewed the studies and extracted data. Overall quality of economic analysis reporting was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Ten prospective studies (including six randomized studies) and nine retrospective studies were eligible. Overall study reporting was poor, publications meeting a median (range) of 61% (46-82%) of CHEERS checklist criteria. An antimicrobial TDM intervention for adult patients was the focus of most studies (n = 18). Variable clinical outcomes were reported, and length of stay was the primary economic outcome for most studies (n = 13). The majority of studies determined that TDM was economically and clinically favourable (n = 14), four studies reporting a cost-reduction in patient sub-populations. Significant improvements in both economic and clinical outcomes may be realized with TDM interventions, particularly when targeted to complex patient populations. Attainment of therapeutic target could serve as a feasible surrogate measure of benefit for hospital-based TDM interventions. However, systematic reporting of economic outcomes is needed to inform investment decisions.

Managing Pruritus in Advanced Chronic Disease.

Even though pruritus affects a significant number of people with chronic disease, it is rarely adequately treated. Drug therapies often rely on antihistamines, which have not shown to be beneficial in systemic pruritus. Hydroxyzine is frequently used to treat pruritus associated with kidney failure. Since Canada's sole manufacturer of hydroxyzine is no longer making this product, this is an ideal time to review the mechanisms of itch in advanced organ failure and the specific therapies that give relief. Although there is literature describing itch in patients with cancer, this article is limited to pathogenesis and treatment of systemic itch secondary to chronic, noncancer diseases. We summarize recent systematic reviews, although the studies included in these reviews are often small, and mostly cohort studies.

Managing Pruritus in Advanced Chronic Disease.

Even though pruritus affects a significant number of people with chronic disease, it is rarely adequately treated. Drug therapies often rely on antihistamines, which have not shown to be beneficial in systemic pruritus. Hydroxyzine is frequently used to treat pruritus associated with kidney failure. Since Canada's sole manufacturer of hydroxyzine is no longer making this product, this is an ideal time to review the mechanisms of itch in advanced organ failure and the specific therapies that give relief. Although there is literature describing itch in patients with cancer, this article is limited to pathogenesis and treatment of systemic itch secondary to chronic, noncancer diseases. We summarize recent systematic reviews, although the studies included in these reviews are often small, and mostly cohort studies.

Trial Participation in Neurodegenerative Diseases: Barriers and Facilitators: A Systematic Review and Meta-Analysis.

Clinical trials in neurodegenerative diseases often encounter selective enrollment and under-representation of certain patient populations. This delays drug development and substantially limits the generalizability of clinical trial results. To inform recruitment and retention strategies, and to better understand the generalizability of clinical trial populations, we investigated which factors drive participation. We reviewed the literature systematically to identify barriers to and facilitators of trial participation in 4 major neurodegenerative disease areas: Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and Huntington disease. Inclusion criteria included original research articles published in a peer-reviewed journal and evaluating barriers to and/or facilitators of participation in a clinical trial with a drug therapy (either symptomatic or disease-modifying). The Critical Appraisal Skills Program checklist for qualitative studies was used to assess and ensure the quality of the studies. Qualitative thematic analyses were employed to identify key enablers of trial participation. Subsequently, we pooled quantitative data of each enabler using meta-analytical models. Overall, we identified 36 studies, enrolling a cumulative sample size of 5,269 patients, caregivers, and health care professionals. In total, the thematic analysis resulted in 31 unique enablers of trial participation; the key factors were patient-related (own health benefit and altruism), study-related (treatment and study burden), and health care professional-related (information availability and patient-physician relationship). When meta-analyzed across studies, responders reported that the reason to participate was mainly driven by (1) the relationship with clinical staff (70% of the respondents; 95% CI 53%-83%), (2) the availability of study information (67%, 95% CI 38%-87%), and (3) the use or absence of a placebo or sham-control arm (53% 95% CI 32%-72%). There was, however, significant heterogeneity between studies (all p < 0.001). We have provided a comprehensive list of reasons why patients participate in clinical trials for neurodegenerative diseases. These results may help to increase participation rates, better inform patients, and facilitate patient-centric approaches, thereby potentially reducing selection mechanisms and improving generalizability of trial results.

Comparison of the efficacy of carelizumab combined with chemotherapy and chemotherapy alone in the induction therapy of locally advanced hypopharyngeal carcinoma

Objective: To compare the efficacy and safety of carrelizumab combined with the modified TPF regimen (docetaxel, cisplatinand capecitabine) and TPF regimen alone in larynx preservation strategy for locally advanced resectable hypopharyngeal squamous cell carcinoma. Methods: A cohort study was conducted. Patients with locally advanced resectable hypopharyngeal carcinoma (cT3-4aN0-3bM0) who were treated at the Eye & ENT Hospital of Fudan University from January 2017 to April 2023 were enrolled in the study. One group was treated with a modified TPF regimen (TPF group) for 2-3 cycles (retrospective data), and the other group was a prospective phase Ⅱ trial with a modified TPF regimen combined with carrelizumab (TPFC group) for three cycles. The patients with complete or partial remission of the primary focus were treated with sequential radical radiotherapy and/or drug therapy. The patients in the TPFC group were treated with carrelizumab at the end of radiotherapy with a maximum of up to 18 doses. The patients with stable or progressive disease were given radical surgery, and those who refused the surgery were given radical chemoradiotherapy. Objective response rate (ORR), overall survival rate, progression-free survival (PFS) rate, larynx preservation rate (LPR), and adverse reactions were compared between the two groups. Results: There were 51 male patients in the TPFC group, with an median age of 57 (35, 69) years. Meanwhile, 44 patients were in the TPF group, among which 43 were male and one was female, with an median age of 62 (46, 70) years. The ORR of the TPFC group was higher than that of the TPF group [82.4% (42/51) vs 63.6% (28/44), P=0.039]. During a median follow-up of 24.4 (18.5, 31.4) months, the TPFC group showed a higher 2-year survival rate (84.8% vs 64.6%, P=0.013) and 2-year LPR (66.6% vs 48.6%, P=0.045) than those in the TPF group. In patients with poor effect of induction therapy for hypopharyngeal carcinoma, surgical combination therapy significantly prolonged the 2-year PFS rate (77.9% vs 18.2%, P<0.001) and 2-year survival rate (76.9% vs 45.5%, P=0.005)than those of non-surgical combination therapy. The incidences of nausea and/or vomiting, reactive cutaneous capillary endothelial proliferation, thyroid dysfunction, and rash were increased in the TPFC group (all P<0.05). There was no treatment-related death. Conclusion: Carrelizumab combined with a modified TPF regimen has good efficacy and safety and can improve the LPR of locally advanced hypopharyngeal carcinoma.

Anticandidal applications of selenium nanoparticles biosynthesized with Limosilactobacillus fermentum (OR553490).

Candida albicans is one of the most dangerous pathogenic fungi in the world, according to the classification of the World Health Organization, due to the continued development of its resistance to currently available anticandidal agents. To overcome this problem, the current work provided a simple, one-step, cost-effective, and safe technique for the biosynthesis of new functionalized anticandidal selenium nanoparticles (Se NPs) against C. albicans ATCC10231 using the cell-free supernatant of Limosilactobacillus fermentum (OR553490) strain. The bacterial strain was isolated from yogurt samples available in supermarkets, in Damietta, Egypt. The mixing ratio of 1:9v/v% between cell-free bacterial metabolites and sodium selenite (5 mM) for 72 h at 37°C were the optimum conditions for Se NPs biosynthesis. Ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), X-ray diffraction (XRD), Zeta analyses, and elemental analysis system (EDS) were used to evaluate the optimized Se NPs. The Se NPs absorption peak appeared at 254 nm. Physicochemical analysis of Se NPs revealed the crystalline-shaped and well-dispersed formation of NPs with an average particle size of 17-30 nm. Se NPs have -11.8mV, as seen by the zeta potential graph. FT-IR spectrum displayed bands of symmetric and asymmetric amines at 3279.36 cm-1 and 2928.38 cm-1, aromatic and aliphatic (C-N) at 1393.32 cm-1 and 1237.11.37 cm-1 confirming the presence of proteins as stabilizing and capping agents. Se NPs acted as a superior inhibitor of C. albicans with an inhibition zone of 26 ± 0.03mm and MIC value of 15 µg/mL compared to one of the traditional anticandidal agent, miconazole, which revealed 18 ± 0.14mm and 75µg/mL. The cytotoxicity test shows that Se NPs have a low toxic effect on the normal keratinocyte (IC50 ≈ 41.5 μg/mL). The results indicate that this green synthesis of Se NPs may have a promising potential to provide a new strategy for drug therapy.

Immunobiologicals in severe asthma: case report

According to the Global Initiative for Asthma (GINA), asthma is a chronic-inflammatory respiratory disease, characterized by limitation of expiratory air flow, dyspnea, wheezing and tachypnea, especially at night or in contact with allergens, climate changes or presence of environmental pollution. Among its subtypes, severe asthma stands out, where the symptomatic condition persists despite optimized treatment at advanced levels. The present study is a case report associated with a literature review on the use of immunobiologicals in the clinical treatment of severe asthma. Female patient, 53 years old, history of late-onset asthma at age 25, with frequent exacerbations, using drug therapy based on inhaled corticosteroid (ICS), long-acting β2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) in a single inhaler associated with the use of oral corticosteroids. After confirming the diagnosis of severe non-allergic eosinophilic asthma of endotype T2, GINA 5, the patient started treatment with mepolizumab and months later she showed significant improvement with the use of the immunobiological 1x/month and use of ICS associated with LABA. 12/12h, without the need for oral corticosteroids and use of rescue medications less than 2x/week.

Approach to the Patient Considering Long-term Antithyroid Drug Therapy for Graves' Disease.

Antithyroid drugs (ATD) are the treatment of choice for the majority of patients with Graves' hyperthyroidism worldwide. However, relapse of hyperthyroidism after withdrawal of arbitrarily chosen conventional 12 to 18 months of therapy is very common. In the last 2 decades, many studies have shown that treatment with long-term ATD (LT-ATD) is effective and safe in the maintenance of euthyroidism. In addition, it has been reported that serum TSH receptor antibody may not decrease permanently before 5 to 6 years of ATD treatment, and clinical trials have shown that ≥5 years of ATD treatment is accompanied by remission in the majority of patients with Graves' hyperthyroidism. The objective of this article is to discuss the optimal time to withdraw of conventional ATD therapy, to illustrate the decision-making of the management of recurrent hyperthyroidism, to review the proper management of LT-ATD, and to generate suggestions for lifelong ATD treatment by discussing 4 scenarios of decision-making in patients with Graves' disease.

Immunobiologicals in severe asthma: case report

According to the Global Initiative for Asthma (GINA), asthma is a chronic-inflammatory respiratory disease, characterized by limitation of expiratory air flow, dyspnea, wheezing and tachypnea, especially at night or in contact with allergens, climate changes or presence of environmental pollution. Among its subtypes, severe asthma stands out, where the symptomatic condition persists despite optimized treatment at advanced levels. The present study is a case report associated with a literature review on the use of immunobiologicals in the clinical treatment of severe asthma. Female patient, 53 years old, history of late-onset asthma at age 25, with frequent exacerbations, using drug therapy based on inhaled corticosteroid (ICS), long-acting β2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) in a single inhaler associated with the use of oral corticosteroids. After confirming the diagnosis of severe non-allergic eosinophilic asthma of endotype T2, GINA 5, the patient started treatment with mepolizumab and months later she showed significant improvement with the use of the immunobiological 1x/month and use of ICS associated with LABA. 12/12h, without the need for oral corticosteroids and use of rescue medications less than 2x/week.

A Comprehensive Review: Pharmacogenomics and Personalized Medicine Customizing Drug Therapy Based on Individual Genetics Profiles.

Numerous factors, such as genetics, environmental factors, and illness determinants, might contribute to an unpleasant pharmaceutical response. In an effort to increase efficacy and safety, as well as to gain a better understanding of drug disposition and clinical consequences, researchers in the two quickly emerging fields of pharmacogenetics (which focuses on single genes) and pharmacogenomics (which focuses on many genes) have studied the genetic personalization of drug response. This is due to the fact that a large number of pharmacological responses seem to be genetically based, and the relationship between medication response and genotype may be important for diagnosis. We now have a better understanding of the genetic basis of individual medication responses because to research on pharmaceuticals and genes. Pharmacogenomics aims to improve patient outcomes by developing personalized medicine by using the diversity of the human genome and how it affects medication response. Translational in nature, pharmacogenomics research encompasses everything from the discovery of genotype-phenotype associations to clinical investigations that might show therapeutic relevance. Though the conversion of pharmacogenomics research findings into clinical practice has been sluggish, advances in the field offer considerable potential for future therapeutic applications in specific people.

Characterization of Exopolysaccharides Having Potential Antiviral Properties from Priestia Aryabattai Strain MK1 and Bacillus sp. Strain MK2.

Viral diseases are a serious threat to humans while themost antiviral drugs have low efficiency and side effects on human health. Therefore, using microbial biopolymers as the drugs alternate to treat viral infections seems cost-effective and human friendly option. In the present study, thirty-four exopolysaccharides (EPSs) producing bacteria were isolated, and EPSs production capacity of five salt-tolerant isolates was determined under 0, 100 and 150 mM NaCl. Among these, two isolates exhibiting high anti-coliphage activity were identified through 16S rRNA gene analysis. Moreover, the EPSs were characterized by Fourier-transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) analysis, and their composition was determined. Five salt-tolerant bacteria (MK1, MK2, MK10, MK22 and MK29) exhibited higher production of EPSs at 100 mM NaCl compared to that under non-saline control. At 100 mM NaCl, the yield of EPSs ranged between 105 and 330mg 100 mL-1 broth. The EPSs produced by the isolates MK1 and MK2 exhibited higher anti-coliphage activity (plaque forming unit decreased from 43 × 106 mL-1 to 3 × 106 and 4 × 106 mL-1, respectively), and were comprised of glucose, fructose, galactose, sucrose, lactose and xylose sugars. FTIR spectroscopy depicted that EPSs are mainly composed of hydroxyl, aliphatic, carboxyl, sulfate and phosphate functional groups, which could have bound coliphage and thus conferred higher anti-coliphage activities to the EPSs. Phylogenetic analysis revealed that MK1 and MK2 isolates formed clades within genus Priestia and Bacillus sequences, respectively. High EPSs production capacity of bacterial isolates under saline condition and high anti-coliphage activity of the EPSs implies that bacterial biopolymers could be useful in antiviral drugs therapy.

Infringement of clinical pharmacist's authority.

Clinical pharmacists are healthcare practitioners who have advanced education and training in comprehensive medication management. Clinical pharmacists work with other members of the healthcare team to manage particular medications or disease states. Even though clinical pharmacists are members of healthcare teams, there are still many cases of challenge in the interprofessional relationship with other healthcare team members, especially related to drug management. Increasing interprofessional communication between physicians and clinical pharmacists within the healthcare system could enhance the role of clinical pharmacists. Earlier studies reported that physicians were comfortable with pharmacists detecting and preventing prescription errors, but were uncomfortable with them recommending drug therapy to patients. Acceptance of pharmacists' suggestions by prescribers is a necessary component of the evaluation of clinical pharmacy services. The role of clinical pharmacists could be improved by increasing interprofessional communication between doctors and clinical pharmacists in the healthcare system.

Cardiac channelopathies in the context of hereditary arrhythmia syndromes

Genetic arrhythmia disorders are rare diseases; however, they are acommon cause of sudden cardiac death in children, adolescents, and young adults. In principle, adistinction can be made between channelopathies and cardiomyopathies in the context of genetic diseases. This paper focuses on the channelopathies long and short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia (CPVT). Early diagnosis of these diseases is essential, as drug therapy, behavioral measures, and if necessary, implantation of acardioverter defibrillator can significantly improve the prognosis and quality of life of patients. This paper highlights the pathophysiological and genetic basis of these channelopathies, describes their clinical manifestations, and comments on the principles of diagnosis, risk stratification and therapy.

Development, validation and long-term evaluation of a liquid chromatography-tandem mass spectrometry method for simultaneous quantification of amiodarone, desethylamiodarone and mexiletine in human plasma and serum

Amiodarone and mexiletine are used for ventricular arrhythmias, for which a combination therapy of both anti-arrhythmic drugs (AADs) is not uncommon. Therapeutic drug monitoring (TDM) can be beneficial for clinical guidance of therapy, especially to correctly identify adverse events. Desethylamiodarone, the active metabolite of amiodarone, accumulates over time and is associated with serious adverse events. Therefore, simultaneous TDM for amiodarone, desethylamiodarone and mexiletine is advantageous in clinical practice. The presented LC-MS/MS method was validated for selectivity, matrix effect, linearity, accuracy, precision, carry-over and stability. The method was continuously evaluated during eight months of clinical use. The method was shown to be linear within the measured range of 0.1 to 10 mg/L for each component. The matrix effect was considered negligible. No interfering responses were found for amiodarone, desethylamiodarone and the isotopic-labeled internal standards. A constant and reproducible within-run contribution of 45.3 %, originating from the system, was identified for mexiletine. The systemic contribution to the peak area of the lowest quantifiable concentration of mexiletine affected the selectivity and carry-over effect measurements. Multiple measurements showed that regression adjusted concentrations were accurate and reproducible, indicating calibration correction was applicable. Sample stability was found to be within limits for all storage conditions and freeze–thaw cycles. Furthermore, long-term method evaluation with external controls resulted in stable measurements with a percentage coefficient of variance between 1.3 % and 6.3 %. The presented practical and reliable method is applicable for clinical TDM and will allow clinical practitioners to guide drug therapy of amiodarone and mexiletine.