Determination of pharmaceuticals in plasma by capillary electrophoresis without sample pretreatment reproducibility, limit of quantitation and limit of detection

Abstract

Pharmaceuticals in human plasma are determined on underivatized fused-silica capillaries by micellar electrokinetic capillary chromatography (MEKC) without sample pretreatment. Our best method to date uses as running buffer a sodium dodecyl sulfate (SDS) containing borate buffer (60 mM with 200 mM SDS) at pH 10. Between runs, proteins adsorbed to the capillary wall are removed by an acetonitrile and SDS-buffer rinsing regimen (50% v/v each). A day-to-day precision for relative peak areas of about 2% relative standard deviation (RSD; n > 40) has been reached. Different rinsing approaches are discussed (salts, enzyme-containing solutions, organic solvents, hydrofluoric acid). The separation system is tested in a concentration range between approximately 100 mg/L-10 mg/L. Correlations between the limit of quantitation, the limit of detection and the signal/noise are discussed. The applicability of the system is demonstrated for the pharmaceuticals acetaminophen, salicylic acid, sulfamethoxazole, tolbutamide, and trimethoprim.

Micellar electrokinetic capillary chromatography as a powerful tool for pharmacological investigations without sample pretreatment: A precise technique providing cost advantages and limits of detection to the low nanomolar range

“…The different approaches are summarized in Table 1. With the most commonly used sodium hydroxide solution (0.1 M), drop-outs, baseline irregularities, current breakdowns and even clogging of the capillary were regularly observed [38]. These results agree with the findings of Thormann et al [36] who collected data of over 450 plasma or serum runs and found the percentage of drop-outs to be about 12% or more, a number that dropped to 5% by a simple threefold dilution of the sample with water.…”

Electrochemical Oxidation and Sensitive Determination of Acetaminophen in Pharmaceuticals at Poly(3,4‐ethylenedioxythiophene)‐Modified Screen‐Printed Electrodes

“…This process has been widely studied using titrimetry [3], spectrophotometry [4], spectrofluorometry [5], high performance liquid chromatography [6], capillary electrophoresis [7], flow-injection method [8], and enzyme-based methods [9]. However, liquid chromatography is time-consuming, and titrimetry and spectrophotometry are not convenient.…”

Pharmacokinetic Investigations with Direct Injection of Plasma Samples: Possible Savings Using Capillary Electrophoresis (CE)

“…The commonly used sodium hydroxide rinsing steps cannot prevent analytical drop outs which are routinely observed (ref. [9] , compare [10,11] ). Second, although matrix interferences within the described "analytical window" are clearly reduced, there are still baseline interferences due to the presence of small endogeneous plasma components (e.g.…”

“…antiepileptics, non-steroidal antiinflammatory drugs (NSAID), antibiotics, barbiturates etc. [4][5][6][7][8][9][10][11] . In these earlier works, high µmolar levels have been determined with reproducibilities in the range of about 2-5% for repeatability (n ≈ 10) and of about 4-12% for interday precision, respectively [7,8] .…”