Evaluation of the dose-related concentration approach in therapeutic drug monitoring of diuretics and β-blockers – drug classes with low adherence in antihypertensive therapy

Ritscher, Sabrina; Hoyer, Milena; Wunder, Cora; Obermüller, Nicholas; Toennes, Stefan W.

doi:10.1038/s41598-019-52164-y

Cited by 20 publications

(34 citation statements)

References 41 publications

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“…The comparison of measured concentrations with published reference ranges exhibited marked deviations, which was expected from previous experiences [13]. Of the 78 trough and peak concentrations measured 19 (24.4%, 33.3% of the 39 peak values only) exceeded the upper therapeutic limit.…”

Section: Patients With Confirmed Adherencementioning

confidence: 50%

“…The current recommendations on pharmacotherapy favor the use of ARBs and CCBs due to their more favorable risk-to-benefit ratio in terms of tolerability (especially ARBs) and prevention of organ damage [24]. Considering this and in order to evaluate the potential of misinterpretation using qualitative methods, a quantitative serum assay for ARBs and CCBs was developed as recently published for β-blockers and diuretics [13]. Individually calculated cut-offs were used for classification of adherence.…”

Section: Discussionmentioning

confidence: 99%

“…Concentrations below or above published therapeutic reference ranges are indicated by "#" or """, concentrations below the lower DRC (c.f. [13]) are indicated by " � ". Positive results of the qualitative urinalysis are marked by "+", negative results by "-".…”

Section: Discussionmentioning

confidence: 99%

“…The analysis procedure was essentially the same as described recently [13], but extended for detection of amlodipine, lercanidipine, valsartan, candesartan and telmisartan.…”

Section: Toxicological Analysis Of Serummentioning

confidence: 99%

“…For β-blockers and diuretics, a therapeutic drug monitoring (TDM) methodology and assessment of patient's adherence based on individually calculated cut-offs has proved successful [13]. This concept utilized pharmacokinetic parameters to calculate cut-offs and covered differing dosage schemes.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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

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Section: Patients With Confirmed Adherencementioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The analysis procedure was essentially the same as described recently [13], but extended for detection of amlodipine, lercanidipine, valsartan, candesartan and telmisartan.…”

Section: Toxicological Analysis Of Serummentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Development, validation, and implementation of an UHPLC–MS/MS method for the quantitation of furosemide in infant urine samples

Vedar

Bamat

Zuppa

et al. 2021

Biomedical Chromatography

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Furosemide is a diuretic drug used to increase urine flow in order to reduce the amount of salt and water in the body. It is commonly utilized to treat preterm infants with chronic lung disease of prematurity. There is a need for a simple and reliable quantitation of furosemide in human urine. We have developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometry method for furosemide quantitation in human urine with an assay range of 0.100-50.0 μg/ml. Sample preparation involved solid-phase extraction with 10 μl of urine.Intra-day accuracies and precisions for the quality control samples were 94.5-106 and 1.86-10.2%, respectively, while inter-day accuracies and precision were 99.2-102 and 3.38-7.41%, respectively. Recovery for furosemide had an average of 23.8%, with an average matrix effect of 101%. Furosemide was stable in human urine under the assay conditions. Stability for furosemide was shown at 1 week (room temperature, 4, À20 and À78 C), 6 months (À78 C), and through three freeze-thaw cycles. This robust assay demonstrates accurate and precise quantitation of furosemide in a small volume (10 μl) of human urine. It is currently being implemented in an ongoing pediatric clinical study.

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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

et al. 2022

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Volumetric absorptive microsampling (VAMS), an emerging microsampling technique, is a promising tool for adherence monitoring. This study focused on development of an analytical methodology to improve VAMS-based strategies for adherence assessment by analyzing angiotensin-converting-enzyme (ACE) inhibitors, loop diuretics, a potassium-sparing diuretic, and a thiazide diuretic. Development included sample preparation, chromatographic conditions, mass spectrometry settings, validation, and demonstrating proof of concept. Quantification of analytes, by name furosemide, hydrochlorothiazide, lisinopril, torasemide, and the active metabolites, canrenone, enalaprilat, and ramiprilat in finger prick blood (FPB), was validated based on international guidelines. Selectivity, carryover, and within/between-run accuracy and precision were in accordance with the recommendations. The matrix effect was evaluated at three different hematocrit levels (HT: 20%, 40%, 60%) and the coefficients of variation did not exceed 15%. Dilution integrity (1:10 and 1:20) was given for all analytes except lisinopril, yet for lisinopril, the therapeutic range was already covered by the calibration range. Long-term stability in VAMS tips was tested for 2 weeks at 24 °C in the dark and revealed no degradation of analytes. The proof of concept was performed by analyzing 35 intakes of ACE-inhibitors and diuretics in 18 VAMS and matched plasma samples. Hereby, determined concentration in FPB and plasma cannot be used interchangeably, and thus specific reference ranges for whole blood must be established. Nevertheless, the VAMS-based strategy was shown to be suitable for assessing adherence of all classes of antihypertensive drugs used in the guidelines to manage hypertension. Graphical abstract

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Evaluation of the dose-related concentration approach in therapeutic drug monitoring of diuretics and β-blockers – drug classes with low adherence in antihypertensive therapy

Cited by 20 publications

References 41 publications

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

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

Development, validation, and implementation of an UHPLC–MS/MS method for the quantitation of furosemide in infant urine samples

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

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