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Table 1.

Validation data: Lower limit of quantification (LLOQ), limit of detection (LOD), intra- and inter-day precision, accuracy, recovery and matrix effects measured using the given quality control levels.

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Table 2.

Mass spectrometry parameters for the detection of calcium channel blockers and angiotensin receptor blockers using LC-MS/MS operated in dynamic MRM mode with two transitions for analytes and one for the corresponding internal standard.

Retention times, MRM transitions and collision energies (CE) are given.

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Table 3.

The data from pharmacokinetic studies refer to healthy volunteers (n = total number of volunteers) with data on bioavailability (f), apparent total clearance (CLt/f) and its standard deviation (SD), average elimination half-life (t½), the mean dose related concentration (DRC) factor with its lower limit for two time intervals between last dose and blood sampling (Δt).

For other values of Δt the formulas below have to be employed. The last column cites the therapeutic reference range as retrieved from Schulz et al. [19].

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Fig 1.

Representative extracted ion chromatograms of internal standards are given in (A) and of all analytes in the lowest calibrator, a blank sample, and trough serum samples of patient #IP 21 on amlodipine (14.8 ng/ml), patient #IP 18 on candesartan (72.0 ng/ml) and lercanidipine (3.2 ng/ml), and patient #IP 23 on lercanidipine (0.6 ng/ml) in (B).

All signals are in equal scale.

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Table 4.

Concentrations of ARBs and CCBs in serum samples of inpatients (IP) shortly before and about 2 h after observed ingestion (trough / peak).

Concentrations below or above published therapeutic reference ranges are indicated by “↓” or “↑”. No concentrations below the lower DRC (lower DRC factor * daily dose) were observed.

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Table 5.

Serum concentrations and qualitative results in urine from corresponding spot samples of outpatients (OP) regarding ARBs and CCBs.

Prescribed dosages and times (Δt) between blood/urine sampling and last dose are given. 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 “-”.

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Fig 2.

Analytical data (extracted ion chromatograms in equal scale) of candesartan in serum and urine.

Patient #OP 14 with a serum concentration above the respective DRC (1.4 ng/ml) but a negative urine analysis result, in contrast to results in two representative patients (#OP 10 and #OP 19) being positive in serum and urine.

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