Quantitative determination of ?-cyclodextrin in human plasma by liquid chromatography/positive ion electrospray mass spectrometry

Abstract

A sensitive and selective method for the determination of α‐cyclodextrin in human plasma is described using β‐cyclodextrin as an internal standard. After protein precipitation with perchloric acid, the analytes were isolated from human plasma by solid‐phase extraction on Bond Elut C18 cartridges. The compounds were chromatographed on a narrow‐bore aminopropyl column (125 × 2 mm i.d., 5 µm) and analyzed by electrospray ionization mass spectrometry in the positive selected‐ion mode using the [M + NH4]+ ion. The lower limit of quantitation was 5 ng ml−1 of human plasma. Linear calibration curves were obtained over the concentration range 5–1000 ng ml−1 of human plasma. The intra‐ and inter‐assay precisions were <18% and the accuracy was <10.5% over the entire concentration range. During the method development, the ionization efficiencies of the analytes in plasma samples originating from different sources were examined to overcome the matrix effect problems caused by co‐eluting endogenous compounds. The method was successfully applied to pharmacokinetic studies in human volunteers. Copyright © 2000 John Wiley & Sons, Ltd.

Liquid chromatography/mass spectrometric bioanalysis of a modified γ‐cyclodextrin (Org 25969) and Rocuronium bromide (Org 9426) in guinea pig plasma and urine: its application to determine the plasma pharmacokinetics of Org 25969

“…It was found to be stable in both matrices. The extraction efficiency of Org 25959 from plasma was not determined because of the matrix effect, which can preclude accurate determination 13…”

“…Others have investigated the ability of cyclodextrins to form inclusion complexes with limited success regarding sensitivity 3,. 12 More recently, Hammes et al 13 investigated the use of LC/MS in positive selected‐ion mode monitoring (SIM) with improved sensitivity.…”

Rapid quantification of 2-hydroxypropyl-β-cyclodextrin in liquid pharmaceutical formulations by 1H nuclear magnetic resonance spectroscopy

“…Given that 2-HP-b-CD carbohydrates contain no chromophores, and that the molar mass is an average mass related to the average substitution degree, classical LC-UV analytical techniques are not applicable for their dosage. More specific approaches were therefore described for the quantification of CDs by using evaporative light scattering detection, mass spectrometry, refractive index detection, pulsed amperometry, colorimetric detection or based on cyclodextrin fluorescence enhancement (Agueros et al, 2005;Hammes et al, 2000;Hui Jiang et al, 2014;Szeman et al, 2002), but to the best of our knowledge, none of them was developed for the quantification of 2-HP-b-CD directly into commercialized liquid pharmaceutical formulations without any extraction or separation steps. Such technique is essential for a rapid and efficient quality control of CDs concentration in formulations when they are used as excipient and more importantly as active ingredient.…”

Quantitative analysis of natural cyclodextrins by high-performance liquid chromatography with pulsed amperometric detection: Application to cell permeation study

“…Furthermore, solid-phase extraction [5,8,10], ultrafiltration [9,12] and centrifugation [13,14] have been used as the pretreatment methods of biological samples containing natural CDs. In the present study, the reversed-phase columns (Zorbax SB-Aq and Zorbax SB-Phenyl) provided good chromatographic performance for the aqueous ␣-CD, ␤-CD and ␥-CD samples.…”

“…In general, the RI and ELSD detectors are of low sensitivity and therefore, they have been applied for the analysis of relatively high concentrations of CDs [2][3][4]. However, a high sensitivity (from micromolar to nanomolar level) for the analysis of CDs has been obtained by using a MS detection [5,6] or PAD detection techniques [7][8][9][10][11][12].…”