Effect on hospital incentive payments and quality performance of a hospital pay for performance (P4P) programme in Belgium.

BACKGROUND: Belgium initiated a hospital pay for performance (P4P) programme after a decade of fixed bonus budgets for "quality and safety contracts". This study examined the effect of P4P on hospital incentive payments, performance on quality measures, and the association between changes in quality performance and incentive payments over time. METHODS: The Belgian government provided information on fixed bonus budgets in 2013-2017 and hospital incentive payments as well as hospital performance on quality measures for the P4P programmes in 2018-2020. Descriptive analyses were conducted to map the financial repercussion between the two systems. A difference-in-difference analysis evaluated the association between quality indicator performance and received incentive payments over time. RESULTS: Data from 87 acute-care hospitals were analyzed. In the transition to a P4P programme, 29% of hospitals received lower incentive payments per bed. During the P4P years, quality performance scores increased yearly for 55% of hospitals and decreased yearly for 5% of hospitals. There was a significant larger drop in incentive payments for hospitals that scored above median with the start of the P4P programme. CONCLUSIONS: The transition from fixed bonus budgets for quality efforts to a new incentive payment in a P4P programme has led to more hospitals being financially impacted, although the effect is marginal given the small P4P budget. Quality indicators seem to improve over the years, but this does not correlate with an increase in reward per bed for all hospitals due to the closed nature of the budget.

UNGAP best practice for improving solubility data quality of orally administered drugs.

An important goal of the European Cooperation in Science and Technology (COST) Action UNGAP (UNderstanding Gastrointestinal Absorption-related Processes, www.ungap.eu) is to improve standardization of methods relating to the study of oral drug absorption. Solubility is a general term that refers to the maximum achievable concentration of a compound dissolved in a liquid medium. For orally administered drugs, relevant information on drug properties is crucial during drug (product) development and at the regulatory level. Collection of reliable and reproducible solubility data requires careful application and understanding of the limitations of the selected experimental method. In addition, the purity of a compound and its solid state form, as well as experimental parameters such as temperature of experimentation, media related factors, and sample handling procedures can affect data quality. In this paper, an international consensus developed by the COST UNGAP network on recommendations for collecting high quality solubility data for the development of orally administered drugs is proposed.

BODIPY-cholesterol can be reliably used to monitor cholesterol efflux from capacitating mammalian spermatozoa.

Capacitation is the final maturation step spermatozoa undergo prior to fertilisation. The efflux of cholesterol from the sperm membrane to the extracellular environment is a crucial step during capacitation but current methods to quantify this process are suboptimal. In this study, we validate the use of a BODIPY-cholesterol assay to quantify cholesterol efflux from spermatozoa during in vitro capacitation, using the boar as a model species. The novel flow cytometric BODIPY-cholesterol assay was validated with endogenous cholesterol loss as measured by mass spectrometry and compared to filipin labelling. Following exposure to a range of conditions, the BODIPY-cholesterol assay was able to detect and quantify cholesterol efflux akin to that measured with mass spectrometry. The ability to counterstain for viability is a unique feature of this assay that allowed us to highlight the importance of isolating viable cells only for a reliable measure of cholesterol efflux. Finally, the BODIPY-cholesterol assay proved to be the superior method to quantify cholesterol efflux relative to filipin labelling, though filipin remains useful for assessing cholesterol redistribution. Taken together, the BODIPY-cholesterol assay is a simple, inexpensive and reliable flow cytometric method for the measurement of cholesterol efflux from spermatozoa during in vitro capacitation.

Migration of Aortic Occlusion Balloons in an in vitro model of the human circulation.

BACKGROUND: Aortic Occlusion Balloons (AOB) are used for hemorrhage control in hemodynamically unstable patients. Stability of an AOB is essential for reliable aortic occlusion. The primary aim of this study is to determine whether different types of AOB migrate after total, intermittent or partial occlusion in a porcine aorta positioned in an in vitro model. MATERIALS AND METHODS: A porcine thoracic aortic section was positioned in a model of the human circulation. Primary and secondary migration was tested in Cook Coda™ 2-9.0-35-120-32 and 2-10-35-140-46, Cook Medical, USA; Rescue balloon™ Tokai RB-167080-E, Tokai Medical Products, Japan; Reliant™ AB46, Medtronic, USA; Russian prototype AOB; ER-REBOA™, Prytime Medical Devices, USA; LeMaitre™ 28 and 45 Aortic Occlusion Catheter, LeMaitre Vascular, USA. These AOB were tested in hypotensive, normotensive and hypertensive scenarios. Migration in total occlusion, intermittent occlusion and partial occlusion was recorded for all AOB. RESULTS: Limited primary migration occurred in all AOB after total occlusion. The Cook Coda™ 2-9.0-35-120-32 balloon showed maximal migration in 1 test cycle. No migration occurred during intermittent occlusion. Kinking occurs in various degrees but does not seem to prevent a successful occlusion of the aorta. No migration occurred during partial occlusion except in the Russian prototype AOB. In a partial occlusion scenario, distal perfusion occurred only with 5 ml remaining in all balloon types. CONCLUSIONS: All AOB were successful in full aortic occlusion. Limited primary migration occurred in all AOB after total occlusion only the Cook Coda™ 2-9.0-35-120-32 balloon showed maximal migration once. No migration occurred during intermittent occlusion, during partial occlusion only the Russian prototype AOB migrated. Stiffness and size of the catheter are important factors in preventing migration and kinking.

Trends in direct oral anticoagulant (DOAC) use: health benefits and patient preference.

In 2012, the Dutch Health Council published a report addressing barriers for an early and broad introduction of direct oral anticoagulants (DOACs). The report raised concerns about the lack of an antidote, adherence, lack of monitoring in the case of overdose and the increased budget impact at DOAC introduction. In the past decade, international studies have shown that DOACs can provide healthcare benefits for a large number of patients. This has led to an increase in the prescription of DOACs, as they are an effective and user-friendly alternative to vitamin K antagonists (VKAs). Unlike VKAs, DOACs do not need monitoring of the international normalized ratio due to more predictable pharmacokinetics. However, the number of prescriptions of DOACs in the Netherlands is still lagging, compared to other European countries. This article highlights the potential health gains in the Netherlands if the use of DOACs were to increase, based on current international experience.

[5-HT3-antagonists as a substitute for metoclopramide and domperidone: a literature review]. / 5-HT3-receptorantagonisten als vervangers van metoclopramide en domperidon.

OBJECTIVE: To investigate whether the anti-emetics metoclopramide and domperidone can be replaced by 5-HT3-antagonists, as side effects restrict use of these dopamine antagonists. DESIGN: Systematic review. METHOD: We searched the Embase and PubMed databases for articles published in the period 1995-October 2015, in which the efficacy or side effects of metoclopramide or domperidone were compared with at least one of the 5-HT3-antagonists ondansetron, granisetron, tropisetron or palonosetron. These had to be randomised controlled clinical studies into the known indications for metoclopramide and domperidone for prevention and treatment of nausea and vomiting. Two reviewers independently selected articles based on the title and abstract, then assessed for eligibility based on the full texts. RESULTS: In total, 56 articles were included in this review. The conclusion in 51 studies was that the efficacy of 5-HT3-antagonists in nausea and vomiting is comparable or even superior to that of metoclopramide. Metoclopramide more often caused extrapyramidal side effects; 5-HT3-antagonists were more likely to cause headaches and constipation. The majority of the studies compared metoclopramide with ondansetron. None of the articles studied palonosetron, and only one study compared domperidone with a 5-HT3-antagonist. CONCLUSION: We found enough evidence to presume that metoclopramide can be replaced by 5-HT3-antagonists for preventing delayed chemotherapy-induced nausea and vomiting and for prophylaxis or treatment of postoperative nausea and vomiting. More research is needed into the other indications and into the substitutability of domperidone.

['Red yeast rice' as a cholesterol-lowering substance?Caution is warranted]. / 'Rode gist rijst' als cholesterolverlager?

- In various non-medical publications, red yeast rice (red fermented rice, RYR) is recommended as a cholesterol-lowering substance. This supplement contains a naturally occurring statin, namely monacolin K.- Patients who wish to use RYR should be advised to only take products from reputable pharmaceutical companies. Pharmacists can provide advice on this.- Users of RYR should be alerted to the potential drug interactions and serious risks associated with its use during pregnancy.- RYR appears to be better tolerated than statins. This difference in tolerance can be traced back to the applied dosages. On average, the daily RYR dosage contains less statin than the standard dosage for statins.- The Netherlands Food and Consumer Product Safety Authority should urgently test the RYR supplements available in the Netherlands to gain more insight into the quality of said products.- Mandatory registration of RYR as an herbal medicine appears necessary to guarantee the quality of, and monacolin levels in, the products and to reduce health risks.

Optimization of vitamin K antagonist drug dose finding by replacement of the international normalized ratio by a bidirectional factor: validation of a new algorithm.

UNLABELLED: ESSENTIALS: We developed a new algorithm to optimize vitamin K antagonist dose finding. Validation was by comparing actual dosing to algorithm predictions. Predicted and actual dosing of well performing centers were highly associated. The method is promising and should be tested in a randomized trial. BACKGROUND: Oral vitamin K antagonists (VKAs) have a narrow therapeutic window and thus require frequent monitoring of its intensity by the international normalized ratio (INR). Improvement of VKA dosing defined as more time in therapeutic range (TTR) can reduce thrombotic disease and bleeding. Computerized decision support programs (CDSs) are used to optimize VKA dosing, but the effects are heterogeneous. CDSs significantly improve the proportion of time in the therapeutic INR range for initiation therapy but not the quality of anticoagulant management in an outpatient setting. One of the major problems of VKA dose finding is that the INR is a ratio and does not present linearity. We developed a new dose-finding algorithm, based on a novel bidirectional factor (BF). This BF is linear transformation of the nonlinear INR. METHODS: We compared the outcomes of the new algorithm, called BF-N, with dose finding performed at three highly ranked Dutch anticoagulation centers, using both acenocoumarol and phenprocoumon. RESULTS: The outcomes of the BF-N algorithm showed a linear correlation with VKA doses of the three centers (y = 1.001x, r(2) 0.999 for acenocoumarol and y = 0.999x, r(2) 0.999 for phenprocoumon), with a standard deviation of 3.83%. The rate of automated dosage proposals increased to 100%. CONCLUSION: The BF-N algorithm performs well in real-life settings and increases the rate of automated dosage proposals. The algorithm can be easily built into existing CDSs. Experienced staff remains necessary for complicated situations. The new algorithm needs to be evaluated in a prospective trial.

[Appropriate choice of drugs in older patients]. / De juiste keuze van geneesmiddelen bij ouderen.

Older patients use many drugs, while there is hardly any information about the effect and safety of these in elderly patients. It appears that only 56%, and 20% of the information required by the European Medicines Agency (EMA) concerning use of medication in the elderly is stated in the patient information leaflet and in the Dutch Pharmacotherapeutic Compass, respectively. The Expertise Centre PHarmacotherapy in Old Persons (Ephor) gathered all available information about drug prescribing in older patients for a number of drug groups from national and international literature, and provided prescribing advice. This information will be made available to users of the Dutch Pharmacotherapeutic Compass, for quick accessibility.

[Detecting inappropriate medication in older people: the revised STOPP/START criteria]. / Onjuist geneesmiddelgebruik bij ouderen opsporen. De herziene STOPP- en START-criteria.

The use of potentially inappropriate medications (PIMs) by older people and potential prescribing omissions (PPOs) represent a serious problem. It increases the risk of adverse drug reactions (ADRs), however it is susceptible to influence in a substantial number of cases. Use of the STOPP/START criteria developed in Ireland to optimise pharmacotherapy of older people reduces the number of ADRs and medication errors. Licensing of new drugs, the increased number of potentially inappropriate drugs, and the availability of new literature were grounds for an update of the first version of the STOPP/START criteria which was published in 2008. In order to develop a screening tool with a broader application, a consensus panel of experts in the field of pharmacotherapy of older people was selected from 14 European countries for the second version of the STOPP/START criteria, including two from the Netherlands. The translation of the second version of the STOPP/START criteria has been adapted to the situation in the Netherlands, partly by omitting drugs that are not licensed in the Netherlands.

[Need for improvement in education on appropriate prescribing in elderly patients]. / Onderwijs in het voorschrijven aan ouderen moet beter.

Prescribing errors can cause great harm to patients. In the Netherlands, it is estimated that 7000 preventable medication-related hospitals admissions occur annually, caused in many cases by prescribing errors. Elderly patients are at greatest risk, since this patient demographic is most likely to be prescribed multiple medications. Robust education on appropriate prescribing is essential for all clinicians with the authority to prescribe. Currently, some issues still require improvement in the Netherlands: a) education continues to focus heavily on basic pharmacology knowledge instead of patient related pharmacotherapy skills, b) an appropriate assessment procedure on pharmacotherapy knowledge and skills is often lacking, c) there is no mandatory requirement for physicians to maintain their knowledge and skills in the field of pharmacotherapy during their working career. In this article we discuss means to improve this situation, with the overall aim to ensure that all vulnerable elderly patients are in safe hands with each physician.

[Interaction between NSAIDs and acetylsalicylic acid disregarded]. / Interactie NSAID's en acetylsalicylzuur genegeerd.

In 2013 the European Medicines Agency declared that diclofenac is contraindicated in patients with arterial thrombotic complications, based on a meta-analysis of randomised controlled trials on the adverse reactions of NSAIDs. The same decision was taken for coxibs some years earlier. The Dutch authorities (CBG/MEB) informed physicians and pharmacists about this decision without taking into account whether these patients were using prophylactic acetylsalicylic acid or not. It has been shown that NSAIDs with high COX-1 affinity like ibuprofen and naproxen cause a pharmacodynamic interaction with the inhibition of thromboxane synthesis by acetylsalicylic acid. This interaction does not occur with relatively COX-2-selective NSAIDs such as coxibs and diclofenac. Therefore, in patients who use acetylsalicylic acid for thromboprophylaxis, contraindicating coxibs or diclofenac is not justified, on the contrary: they are preferable.

Simultaneous determination of rifampicin, clarithromycin and their metabolites in dried blood spots using LC-MS/MS.

INTRODUCTION: Rifampicin (RIF) and clarithromycin (CLR) are common drugs for the treatment of infections like Mycobacterium tuberculosis and Mycobacterium ulcerans. Treatment for these diseases are long-term and the individual pharmacokinetic variation, drug-drug interactions or non-adherence may introduce sub-therapeutic exposure or toxicity. The application of therapeutic drug monitoring (TDM) can be used to ensure efficacy and avoid toxicity. With the use of dried blood spot (DBS), TDM may be feasible in rural areas. During DBS method development, unexpected interactions or matrix effects may be encountered due to endogenous components in the blood. Another complication compared to plasma analysis is that RIF can form chelate complexes with ferric ions or can bind with hemes, which are potentially present in the extracts of dried blood spots. METHODS: The investigation focused on the interaction between RIF and the endogenous components of the DBS. The use of ethylenediaminetetraacetic acid (EDTA) and deferoxamine (DFX) as chelator agents to improve recoveries and matrix effects were investigated. A rapid analytical method was developed and validated to quantify RIF and CLR and their active metabolites desacetyl rifampicin (DAc-RIF) and 14-hydroxyclarythromcin (14OH-CLR) in DBS samples. A clinical application study was performed in tuberculosis patients by comparing DBS concentrations with plasma concentrations. RESULTS: The interaction between RIF and the DBS matrix was avoided using the complexing agents EDTA and DFX, which improved recoveries and matrix effects. The developed sample procedure resulted in a simple and fast method for the simultaneous quantification of RIF, CLR and their metabolites in DBS samples. High stability was observed as all four substances were stable at ambient temperature for 2 months. Deming regression analysis of the clinical application study showed no significant differences for RIF, DAc-RIF, CLR and 14OH-CLR between patient plasma and DBS analysis. The slopes of the correlation lines between DBS and plasma concentrations of RIF, DAc-RIF, CLR and 14OH-CLR were 0.90, 0.99, 0.80 and 1.09 respectively. High correlations between plasma and DBS concentrations were observed for RIF (R(2)=0.9076), CLR (R(2)=0.9752) and 14OH-CLR (R(2)=0.9421). Lower correlation was found for DAc-RIF (R(2) of 0.6856). CONCLUSION: The validated method is applicable for TDM of RIF, CLR and their active metabolites. The stability of the DBS at high temperatures can facilitate the TDM and pharmacokinetic studies of RIF and CLR even in resource limited areas. The role of EDTA and DFX as complexing agents in the extraction was well investigated and may provide a solution for potential applications to other DBS analytical methods.

Suspected tuberculosis case detection and referral in private pharmacies in Viet Nam.

SETTINGS: Private pharmacies in Hanoi, Viet Nam. OBJECTIVES: To explore the response of health care providers (HCPs) in private pharmacies to suspected tuberculosis (TB) patients. METHODS: A simulated patient method combined with an interview in 128 randomly selected private pharmacies and 10 private pharmacies near TB hospitals. RESULTS: In the simulated patient method and interview, respectively 59 (46%) and 70 (55%) of HCPs referred the TB suspect to general health care. Only 11 (9%) referred the simulated patient to a TB care facility. Fifty-two (42%) of the HCPs identified suspected TB from a fictitious case described on paper; 34 (27%) were aware that free treatment was provided under the National Tuberculosis Programme (NTP). Knowledge about free NTP treatment predicted a higher rate of direct referrals to TB facilities (OR 5.80, 95%CI 1.88-19.62) and greater ability to identify suspected TB from a fictitious case on paper (OR 5.14, 95%CI 2.36-11.73). Pharmacies with Good Pharmacy Practice (GPP) certification were less likely to refer simulated patients to TB facilities than non-GPP pharmacies (OR 0.10, 95%CI ≤0.01-0.79). CONCLUSIONS: Nearly half of HCPs in private pharmacies do not refer TB suspects, possibly contributing to delays in diagnosis and treatment. Knowledge about free NTP treatment predicted better performance of HCPs.

Dried blood spot analysis for therapeutic drug monitoring of linezolid in patients with multidrug-resistant tuberculosis.

Linezolid is a promising antimicrobial agent for the treatment of multidrug-resistant tuberculosis (MDR-TB), but its use is limited by toxicity. Therapeutic drug monitoring (TDM) may help to minimize toxicity while adequate drug exposure is maintained. Conventional plasma sampling and monitoring might be hindered in many parts of the world by logistical problems that may be solved by dried blood spot (DBS) sampling. The aim of this study was to develop and validate a novel method for TDM of linezolid in MDR-TB patients using DBS sampling. Plasma, venous DBS, and capillary DBS specimens were obtained simultaneously from eight patients receiving linezolid. A DBS sampling method was developed and clinically validated by comparing DBS with plasma results using Passing-Bablok regression and Bland-Altman analysis. This study showed that DBS analysis was reproducible and robust. Accuracy and between- and within-day precision values from three validations presented as bias and coefficient of variation (CV) were less than 17.2% for the lower limit of quantification and less than 7.8% for other levels. The method showed a high recovery of approximately 95% and a low matrix effect of less than 8.7%. DBS specimens were stable at 37°C for 2 months and at 50°C for 1 week. The ratio of the concentration of linezolid in DBS samples to that in plasma was 1.2 (95% confidence interval [CI], 1.12 to 1.27). Linezolid exposure calculated from concentrations DBS samples and plasma showed good agreement. In conclusion, DBS analysis of linezolid is a promising tool to optimize linezolid treatment in MDR-TB patients. An easy sampling procedure and high sample stability may facilitate TDM, even in underdeveloped countries with limited resources and where conventional plasma sampling is not feasible.

NMDA receptor genotypes associated with the vulnerability to develop dyskinesia.

Dyskinesias are involuntary muscle movements that occur spontaneously in Huntington's disease (HD) and after long-term treatments for Parkinson's disease (levodopa-induced dyskinesia; LID) or for schizophrenia (tardive dyskinesia, TD). Previous studies suggested that dyskinesias in these three conditions originate from different neuronal pathways that converge on overstimulation of the motor cortex. We hypothesized that the same variants of the N-methyl-D-aspartate receptor gene that were previously associated with the age of dyskinesia onset in HD were also associated with the vulnerability for TD and not LID. Genotyping patients with LID and TD revealed, however, that these two variants were dose-dependently associated with susceptibility to LID, but not TD. This suggested that LID, TD and HD might arise from the same neuronal pathways, but TD results from a different mechanism.

Statistical description of turbulent dispersion.

We derive a comprehensive statistical model for dispersion of passive or almost passive admixture particles such as fine particulate matter, aerosols, smoke, and fumes in turbulent flow. The model rests on the Markov limit for particle velocity. It is in accordance with the asymptotic structure of turbulence at large Reynolds number as described by Kolmogorov. The model consists of Langevin and diffusion equations in which the damping and diffusivity are expressed by expansions in powers of the reciprocal Kolmogorov constant C_{0}. We derive solutions of O(C_{0}^{0}) and O(C_{0}^{-1}). We truncate at O(C_{0}^{-2}) which is shown to result in an error of a few percentages in predicted dispersion statistics for representative cases of turbulent flow. We reveal analogies and remarkable differences between the solutions of classical statistical mechanics and those of statistical turbulence.

Dried blood spots: a new tool for tuberculosis treatment optimization.

Tuberculosis (TB) is a high-burden infectious disease, especially in low and middle-income countries. The efforts to eliminate this disease are challenged by the emergence of multidrug resistance and TB-HIV coinfection. The cumulative knowledge on pharmacokinetics/ pharmacodynamics of antituberculosis agents has recently encouraged therapeutic drug monitoring (TDM) in patient care. However, logistical problems related to conventional sampling limit the application of TDM in research-oriented institutions. Dried blood spot (DBS) compared with conventional venous blood sampling has the advantages of easier sampling, storage and transportation, thus enabling the application of TDM even in remote areas. In addition, DBS with its lower biohazardous risk can be safely performed in a high HIV prevalence area, which also tends to have a high TB burden. Another benefit of DBS sampling is that it requires a smaller blood volume than conventional sampling and is highly recommended for application in pediatric TB. A limitation of DBS is that additional considerations are required for analysis method development and validation. The accuracy of the DBS method is influenced by a number of factors that need to be thoroughly examined in method development and validation. Further, the agreement between DBS and plasma/serum concentrations is not always understood and further investigations are required.

Doctors' beliefs and knowledge on corticosteroid-induced osteoporosis: identifying barriers to improve prevention.

WHAT IS KNOWN AND OBJECTIVE: Despite the availability of effective treatments for the management of corticosteroid-induced osteoporosis (CIOP), the condition is undertreated. Our objective was to assess prescribers' knowledge and likely prescribing patterns concerning the diagnosis and treatment of CIOP. Another goal was to identify key barriers to the use of preventive therapy in patients using long-term corticosteroids. METHODS: We used a postal survey of general practitioners (GPs) and specialists in the Netherlands. The survey comprised of questions on: demographic data, perceived barriers to the use of preventive therapy for CIOP, and knowledge of diagnosis and treatment of CIOP. Case scenarios were questioned to assess practice patterns. RESULTS: Responding prescribers correctly answered an average of 55% of knowledge questions and 69% of case scenarios. Multiple questions and cases showed that knowledge on the use of bone mineral density (BMD) determination was poor. BMD was determined in patients who, according to the national osteoporosis guideline, should be treated with bisphosphonates independent of BMD. Moreover, only 18% of doctors correctly answered that the BMD cutoff in CIOP patients is a T-score of ≤-1 or ≤-1·5. Key barriers identified were: (i) GPs, significantly more than specialists, consider prescription of preventive therapy the responsibility of another doctor; (ii) discontinuation of anti-resorptive medication due to adverse effects and (iii) the reluctance to prescribe preventive therapy in patients already prescribed multiple medications. WHAT IS NEW AND CONCLUSION: Doctors did not identify many barriers to the prescribing of anti-resorptive therapies. Lack of knowledge, especially concerning use of BMD-results, likely led to the under-treatment of the presented patients.

Determination of moxifloxacin in dried blood spots using LC-MS/MS and the impact of the hematocrit and blood volume.

Moxifloxacin (MFX) is a potential oral agent use in the treatment of multidrug-resistance tuberculosis (MDR-TB). Due to variability in pharmacokinetics and in vitro susceptibility of causative bacteria, therapeutic drug monitoring (TDM) of MFX is recommended. Conventional plasma sampling for TDM is facing logistical challenges, especially in limited resource areas, and dried blood spots (DBS) sampling may offer a chance to overcome this problem. The objective of this study was to develop a LC-MS/MS method for determination of MFX in dried blood spots (DBS) that is applicable for TDM. The influence of paper type, the hematocrit (Hct) and the blood volume per spot (V(b)) on the estimated blood volume in a disc (V(est)) was investigated. The extracts of 8mm diameter discs punched out from DBS were analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS) with cyanoimipramin as internal standard. The method was validated with respect to selectivity, linearity, accuracy, precision, sensitivity, recovery and stability. The effect of Hct and V(b) on LC-MS/MS analytical result was also investigated. The relationship between MFX concentrations in venous and finger prick DBS and those in plasma was clinically explored. V(est) was highly influenced by Hct while the effect of V(b) appeared to be different among paper types. Calibration curves were linear in the range of 0.05-6.00 mg/L with inter-day and intra-day precisions and biases of less than 11.1%. The recovery was 84.5, 85.1 and 92.6% in response to blood concentration of 0.15, 2.50 and 5.00 mg/L, respectively. A matrix effect of less than 11.9% was observed. MFX in DBS was stable for at least 4 weeks at room condition (temperature of 25°C and humidity of 50%). A large range of Hct value produced a significant analytical bias and it can be corrected with resulting DBS size. A good correlation between DBS and plasma concentrations was observed and comparable results between venous DBS and finger prick DBS was attained. This fully validated method is suitable for determination of MFX in dried blood spot and applicable for TDM.