Non-adherence to cardiovascular pharmacotherapy in Iraq assessed using 8-items Morisky questionnaire and analysis of dried blood spot samples

open access journalThe study evaluated the non-adherence to selected cardiovascular medications, atenolol, atorvastatin, bisoprolol, diltiazem, lisinopril, simvastatin and valsartan in Iraqi patients by applying a standardized Morisky questionnaire (8-MMAS) and by measuring therapeutic drug concentrations in dried blood spots (DBS) analyzed by liquid chromatography - high resolution mass spectrometry (LC-HRMS). Sixty-nine patients, on continued use of one or more of the selected drugs, were evaluated. The questionnaire showed that 21.7% of participants were non-adherent whereas DBS analysis showed that 49.3% were non-adherent to their medications. No significant correlation between medication non-adherence and gender was detected, but adherence was negatively correlated with the number of medications in the regimen. The 8-items questionnaire was unable to differentiate non-adherence to multiple medications in the prescribed pharmacotherapy regimens. DBS is an alternative to conventional methods to monitor non-adherence objectively. Agreement between the two approaches was weak (Kappa =0.269, p-value 0.05)

Adherence to cardiovascular pharmacotherapy by patients in Iraq: a mixed methods assessment using quantitative dried blood spot analysis and the 8-item Morisky Medication Adherence Scale

open access articleThis study evaluated the adherence to prescribed cardiovascular therapy medications among cardiovascular disease patients attending clinics in Misan, Amara, Iraq. Mixed methods were used to assess medication adherence comprising the Arabic version of the eight-item Morisky Medication Adherence Scale (MMAS-8) and determination of drug concentrations in patient dried blood spot (DBS) samples by liquid chromatography-high resolution mass spectrometry. Three hundred and three Iraqi patients (median age 53 years, 50.5% female) who had been taking one or more of the nine commonly prescribed cardiovascular medications (amlodipine, atenolol, atorvastatin, bisoprolol, diltiazem, lisinopril, losartan, simvastatin and valsartan) for at least six months were enrolled. For each patient MMAS-8 scores were determined alongside drug concentrations in their dried blood spot samples. Results from the standardized questionnaire showed that adherence was 81.8% in comparison with 50.8% obtained using the laboratory-based microsample analysis. The agreement between the indirect (MMAS-8) and direct (DBS analysis) assessment approaches to assessing medication adherence showed significantly poor agreement (kappa = 0.28, P=0.001). The indirect and direct assessment approaches showed no significant correlation between nonadherence to prescribed cardiovascular pharmacotherapy and age and gender, but were significantly associated with the number of medications in the patient’s treatment regimen (MMAS-8: Odds Ratio (OR) 1.947, 95% CI, P=0.001; DBS analysis: OR 2.164, 95% CI, P=0.001). The MMAS-8 results highlighted reasons for nonadherence to prescribed cardiovascular pharmacotherapy in this patient population whilst the objective DBS analysis approach gave valuable information about nonadherence to each medication in the patient’s treatment regimen. DBS sampling, due its minimally invasive nature, convenience and ease of transport is a useful alternative matrix to monitor adherence objectively in Iraq to cardiovascular pharmacotherapy. This information combined with MMAS-8 can provide clinicians with an evidence-based novel approach to implement intervention strategies to optimise and personalise cardiovascular pharmacotherapy in the Iraqi population and thereby improve patient health outcomes

Quantitative LC-HRMS determination of selected cardiovascular drugs, in dried blood spots, as an indicator of adherence to medication

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Dried blood spot (DBS) sampling was investigated as a means of obtaining micro-volume blood samples for the quantitative analyses of ten commonly UK prescribed cardiovascular drugs as an indicator of medication adherence. An 8 mm disc was punched out from each DBS from calibration, quality control and volunteer samples and extracted using methanol containing the internal standard. Each extract was evaporated to dryness, the residue reconstituted in methanol:water (40:60 v/v) containing 0.1% formic acid and analysed by LC-HRMS. Chromatography was performed using gradient elution on a Zorbax Eclipse C18 HD 100 mmx2.1 mm, 1.8 µm pore size column with the column oven temperature at 40˚C. Flow rate of the mobile phase was 0.6ml/min with a run time of 2.5 min. Electrospray positive ionization was used for MS detection. Drug recoveries from spiked blood spots were 68% for simvastatin and ≥ 87% for all other target drugs. Compound specificity was obtained operating the MS with a 5ppm mass window. The LC-HRMS method was validated, with results for accuracy and precision within acceptable limits; analytes were stable at room temperature for at least 10 weeks and different blood spot volumes and haematocrit values had no significant effect. The LC-HRMS assay was used to analyse DBS samples from volunteers, some of whom were prescribed one or more of the target drugs. In results from 37 volunteers the assay successfully identified volunteers who were known to be either adherent or nonadherent; confirmed the correct drug/drugs for multiple prescriptions; demonstrated no false positives from other cardiovascular drugs; revealed several examples of unsuspected non-adherence. These results indicated that the developed assay was suitable for trials with patients

Quantitative screening of the pharmaceutical ingredient for the rapid identification of substandard and falsified medicines using reflectance infrared spectroscopy

open access journalThe World Health Organization suggests that approximately 10% of medicines worldwide are either falsified or substandard with higher figures in low and middle income countries. Such poor quality medicines can seriously harm patients and pose a threat to the economy worldwide. This study investigates attenuated total reflectance-fourier transform infrared (ATR-FTIR) spectroscopy as a simple and rapid method for determination of drug content in tablet dosage forms. Paracetamol was used as the model pharmaceutical ingredient. Spectra of standard mixtures of paracetamol with different excipients formed the basis for multivariate PLS based quantitative analysis of simulated tablet content using different selected infrared absorbance bands. Calibration methods using ATR-FTIR were compared with the ATR-FTIR and conventional ultraviolet spectroscopic analyses of real tablet samples and showed that the paracetamol/microcrystalline cellulose mixtures gave optimum results for all spectral bands tested. The quantitative data for band 1524-1493cm-1 was linear (R2 ˃ 0.98; LOQ ≥ 10%w/w tablet). Global examples of paracetamol tablets were tested using this protocol and 12% of the tablet samples examined was identified as substandard. Each sample analysis was completed in just a few minutes. ATR-FTIR can therefore be used in the rapid screening of tablet formulations. The simplicity of the proposed method makes it appropriate for use in low and middle income countries where analytical facilities are not available

Counterfeit Tablet Investigations: Can ATR FT/IR Provide Rapid Targeted Quantitative Analyses?

Counterfeit medicines are now a global public health problem. In developed countries up to 1% of medicines are reported to be counterfeit whilst in developing countries the level is ~30-40%. In this research the potential of Attenuated Total Reflection (ATR) FT/IR techniques to provide rapid quantitative analyses of suspect tablet formulations is reported. Unlike conventional tablet analyses where several tablets are crushed and solvent extracted, ATR FT/IR methods require that only a single tablet be crushed prior to analysis. This provides a considerable time saving over the solvent extraction protocols cited in the British Pharmacopoeia. Reference ATR FT/IR spectra of the active pharmaceutical ingredient (API) and excipients, from crushed tablets, were recorded for identification purposes. Quantitative data was obtained from ATR FT/IR spectra of calibrated mixtures of the API in the excipients. Tablet samples from various countries, India, Africa, China, Belgium and the UK were examined.Initial results showed the API could be identified down to ca 5% w/w of the tablet. Quantification was linear with selected characteristic peak areas for each API/excipient mixture. The analysis of the tablet samples generally showed good agreement with expectation. This was confirmed by conventional extractive analyses followed by UV quantification. ATR FT/IR can therefore identify counterfeit tablets rapidly without the need for solvents. Whilst LCMS/ MS and NMR techniques may be the ‘gold standards’ of the analytical world they are of much reduced value in sub-Saharan African countries whereas a portable ATR FT/IR may prevent the use of counterfeit antimalarial tablets and contribute to improvements in patient health

Hyphenated mass spectrometry techniques for assessing medication adherence: advantages, challenges, clinical applications and future perspectives

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Nonadherence to prescribed pharmacotherapy is an understated public health problem globally and is costing many patients their chance to return to good health and healthcare systems billions. Clinicians need an accurate assessment of adherence to medications to aid the clinical decision-making process in the event of poor patient progress and to maximize the patient health outcomes from the drug therapies prescribed. An overview of indirect and direct methods used to measure medication adherence is presented, highlighting the potential for accurate measuring of drugs in biological samples using hyphenated mass spectrometry techniques to provide healthcare professionals with a reliable evidence base for clinical decision making. In this review we summarise published applications of hyphenated mass spectrometry techniques for a diverse range of clinical areas demonstrating the rise in the use of such direct methods for assessing medication adherence. Although liquid chromatography-tandem mass spectrometry methods using plasma, serum and urine samples are the most popular, in recent years increased attention has been given to liquid chromatography high-resolution mass spectrometry methods and alternative biosample matrices including hair, saliva and blood microsamples. The advantages and challenges of using hyphenated mass spectrometry techniques to address this healthcare problem are also discussed alongside future perspectives

LC-HRMS analysis of dried blood spot samples for assessing adherence to cardiovascular medications

Research suggests that ~60% of patients prescribed cardiovascular drugs do not take their medication correctly. The analysis of dried blood spot samples (DBS) by liquid chromatography-high resolution mass spectrometry (LC-HRMS) for assessing medication adherence to candidate therapeutic drugs used in cardiovascular therapy was investigated. Specificity using this analytical method was based on the measurement at the accurate mass to charge ratio of the target analyte. To evaluate the method 8mm discs were punched from each DBS and extracted followed by subjecting to LC-HRMS analysis. Trials on 6 commonly UK used cardiovascular drugs are reported demonstrating the ability of the system to detect the target analytes during the 24 hour repeat prescription cycle. Samples from volunteers with confirmed adherence were used to validate the response from the system as were samples from volunteers receiving no medication. No false positives were observed and adherence assessment for bisoprolol, ramipril, amlodipine, valsartan, doxasozin and simvastatin was demonstrated using the LC-HRMS method. Furthermore examples of incorrect adherence were identified

Volumetric absorptive microsampling (VAMS) coupled with high-resolution, accurate-mass (HRAM) mass spectrometry as a simplified alternative to dried blood spot (DBS) analysis for therapeutic drug monitoring of cardiovascular drugs

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Here, volumetric absorptive microsampling (VAMS), used for the measurement of cardiovascular drugs, is compared against conventional dried blood spot (DBS) card sampling to evaluate adherence to prescribed medication. Volumetric absorptive microsampling (VAMS) is an attractive alternative to plasma sampling for routine drug monitoring and potentially overcomes haematocrit issues associated with quantitative bioanalysis of conventional dried blood spots. A quantitative VAMS-based LC-HRAM MS assay for atenolol, lisinopril, simvastatin and valsartan was developed and validated. The assay demonstrated acceptable linearity, selectivity, accuracy, precision, recovery and insignificant matrix effects with no impact of haematocrit on assay accuracy. Volunteers provided both VAMS and DBS 903 card samples (the current standard) to allow comparison of the two methods and demonstrate the potential utility of VAMS. Analysis of VAMS samples correctly identified drugs in volunteers known to be adherent, and found no false positives from volunteers known to be taking no medication. There was a strong correlation between the two sampling systems confirming the utility of VAMS. Therapeutic drug monitoring (TDM) can assist clinicians in deciding how to proceed with treatment in the event of poor improvement in patient health. VAMS could offer a potentially more efficient method of sample collection, with fewer rejected samples than the DBS approach