Rapid gas chromatography/mass spectrometry quinine determination in plasma after automated solid‐phase extraction

Abstract

The combined use of an automatic solid-phase extraction (SPE) apparatus with Oasis MCX cartridges and gas chromatography/mass spectrometry (GC/MS) to rapidly quantify quinine in biological samples with cyproheptadine as the internal standard is described. The selected ion monitoring mode, with the quantification ions m/z 136 and 287 (qualifier ions: m/z 261, 381 and 215, 96), allows the estimation of quinine levels, respectively. Separation was completed within 12.7 min. Excellent linearity was found up to 10 000 microg/L of plasma. The limit of detection (LOD) was 12.2 microg/L and the limit of quantification (LOQ) was 40.6 microg/L. High reproducibility (intra-assay CV range 1.9-4.3%, inter-assay CV range 2.2-11.3%) and accuracy values (intra-assay range 83.2-103.7%, inter-assay range 86.8-103.7%) were obtained. Recoveries were concentration-independent (97.2% and 89.8% for 4000 and 10 000 microg/L, respectively). This sensitive, simple assay for quinine in various matrices meets the current requirements for bioanalytical assays and may be used to monitor quinine levels in patients developing severe malaria with acute renal failure during hemofiltration. The optimal quinine dose in this situation is not really established and to improve clinical care, quinine concentrations might be explored to improve efficacy and minimise potential toxicity.

Ultrasound Assisted Dispersive Liquid–Liquid Microextraction Followed by Injector Port Silylation: A Novel Method for Rapid Determination of Quinine in Urine by GC–MS

“…In order to find out the effect of pH on extraction efficiency of DLLME for QN, three QN spiked samples were extracted at pH 2, 7 and 10 adjusted with the help of either 5M HCl or 5M NaOH. Since QN is a basic drug (pKa = 8.52), alkaline pH has facilitated its extraction by DLLME procedure [9].…”

“…We used BSTFA with 1% TMCS as stimulant for IPS of QN [9]. Initially, the effect of injector port temperature, which can also be regarded as reaction temperature, was studied for QN.…”

“…The mild symptoms include tinnitus, headache and hearing impairment (reversible), while more severe symptoms include vertigo, abdominal pain, vomiting, loss of vision, and so on [22,23]. Some methods based on GC-MS and HPLC have been reported in literature for determination of QN in various matrices [8,9]. HPLC is the most commonly used chromatographic technique for QN in pharmaceutical formulations and biological samples, but the major disadvantage associated with this technique is high detection limits [24,25].…”

“…Several extraction methods such as liquid-liquid extraction (LLE), SPE and solid-phase microextraction (SPME) were reported in the literature [8][9][10]. These techniques suffer with limitations such as: use of large amounts of solvents, tedious and labor-intensive procedures for LLE; multistep process and contamination issues for SPE; and, use of fragile fibers in SPME extraction making it d ifficult for routine ana lysis.…”

“…HPLC is the most commonly used chromatographic technique for QN in pharmaceutical formulations and biological samples, but the major disadvantage associated with this technique is high detection limits [24,25]. On the other hand, GC-MS ana lysis of QN requires derivatization to convert it into nonpolar and volatile derivative, which is achieved by reacting QN with BSTFA [8,9,26]. The sensitivity of GC-MS (12.2 ng/ml) after derivatization is significantly greater to the s ensitivity obtained by HPLC (0.1 µg/ml) [9,25].…”