Benefit of serum drug monitoring complementing urine analysis to assess adherence to antihypertensive drugs in first-line therapy

Abstract

With obesity having doubled in the last decade, hypertension is on the rise. In one-third of hypertensive patients the metabolic syndrome is present. This might be one factor for the increasing number of prescriptions for angiotensin receptor blockers and calcium-channel blockers besides a more favorable risk-to-benefit ratio. The aim of the present study was to evaluate a therapeutic drug monitoring (TDM) method for assessment of adherence based on cutoffs in inpatients and to compare it to an established urine drug screening in outpatients. A method for quantification of calcium-channel blockers and angiotensin receptor blockers using high-performance liquid chromatography-tandem mass spectrometric analysis (LC-MS/MS) was developed and validated. The method was applied to serum samples of 32 patients under supervised medication to establish cutoff values for adherence assessment based on dose-related concentrations (DRC, calculated from pharmacokinetic data). Furthermore, corresponding urine and blood samples of 42 outpatients without supervised medication were analysed and the results compared with regard to adherence assessment. All serum concentrations measured for amlodipine (n = 40), lercanidipine (n = 14), candesartan (n = 10), telmisartan (n = 4) and valsartan (n = 10) in inpatients were above the patient specific lower DRC confirming adherence. Of 42 outpatients the identification of analytes in urine as well as the quantification in serum exhibited differing results. According to urinalysis, adherence was demonstrated in only 87.0% of prescriptions, compared to 91.3% for serum analyses. Differences were observed for amlodipine, lercanidipine and candesartan which can be explained by a higher specificity of the serum analysis approach due to pharmacokinetics. The present study confirms that assessing adherence based on serum drug concentrations with individually calculated lower DRCs is more accurate than using qualitative urine analysis. In particular, drugs with low bioavailability, low renal excretion or high

Development, validation, and application of a quantitative volumetric absorptive microsampling–based method in finger prick blood by means of LC-HRMS/MS applicable for adherence monitoring of antipsychotics

“…Assessing adherence based on serum drug concentrations to complement urine analysis is expected to be more accurate than urine analysis alone, particularly when using the so-called dose-related concentration approach as proposed, e.g., by Ritscher et al [ 24 ]. In general, drugs with low bioavailability, low renal excretion, or underlying extensive metabolism may be underestimated concerning their adherence when using qualitative urine analysis alone.…”

“…So far and to the best of our knowledge, no research article demonstrating the feasibility of VAMS for adherence monitoring was published. Therefore, the aim of this study was to develop and evaluate a VAMS-based strategy for adherence monitoring of antipsychotics in FPB by using drug concentrations to complement qualitative urine analysis [ 24 ]. Analysis should be done by means of LC-HRMS/MS and the whole quantitative workflow should be validated in accordance with international guidelines [ 25 , 26 ].…”

Innate immunity impacts social-cognitive functioning in people with multiple sclerosis and healthy individuals: Implications for IL-1ra and urinary immune markers

“…However, we controlled for creatinine levels to minimise potential confounder variables such as fluid consumption and age. Another possible explanation is based on the generalised assumption that increased serum metabolite concentration will result in increased urine metabolite excretion ( Ritscher et al., 2020 ). However, while this may hold true for healthy individuals, in the context of MS or an alternative disease state, the possible incapacity to excrete these inflammatory mediators as efficiently as healthy individuals, may have resulted in these findings.…”

Closing the gap — development of an analytical methodology using volumetric absorptive microsampling of finger prick blood followed by LC-HRMS/MS for adherence monitoring of antihypertensive drugs

“…A study by Gupta et al demonstrated that liquid chromatography-mass spectrometry (LC-MS)-based analyses of urine or blood of non-adherent patients improve their adherence with consecutive meaningful reductions in blood pressure [10]. Hereby, assessing adherence based on blood concentrations with individually calculated lower dose-related concentrations (DRC) is more accurate than using qualitative analysis alone [11,12]. Up to date, several LC-MS methods for the quantification of AHD exist [13][14][15][16] but they are based on blood, plasma, or serum needing venipuncture, which can cause discomfort and anxiety and requires healthcare professionals.…”