Determination of the stereoisomers of hydroxychloroquine and its major metabolites in plasma and urine following a single oral administration of racemic hydroxychloroquine

doi:10.1016/S0049-0172(10)80011-3

Seminars in Arthritis and Rheumatism

Volume 23, Issue 2, Supplement 1, October 1993, Pages 74-81

https://doi.org/10.1016/S0049-0172(10)80011-3 Get rights and content

Plaquenil (hydroxychloroquine, HCQ; Sanofi Winthrop Pharmaceuticals, New York, NY) is a stereoisomeric drug administered as a racemic (50: 50) mixture of two isomeric forms—(+) and (-) HCQ. To correlate clinical efficiency accurately with dose, it is necessary to determine the fate of both isomers. This will allow for the optimization of clinical dosing. A method has been developed for the quantitation of (+) and (-) HCQ and its major metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdes-ethylchloroquine (BDCQ), in plasma and in urine. Application of this method in a preliminary study in four human volunteers is reported. After a single oral dose of 200 mg of Plaquenil, the average enantiomeric ratio of (+) to (-) HCQ was approximately 1 over an 8-hour period. However, the average cumulative 48-hour excretion of HCQ, DHCQ, and DCQ showed steroselective excretion.

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Square-wave voltammetric determination of hydroxychloroquine in pharmaceutical and synthetic urine samples using a cathodically pretreated boron-doped diamond electrode
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Citation Excerpt :
For the quantification of HCQ in pharmaceutical tablets, the British Pharmacopoeia recommends the use of potentiometric titration in non-aqueous media [10]. Most of the described analytical procedures for the determination of HCQ in pharmaceutical formulations employ chromatographic techniques [11–15], which may have disadvantages such as the need of sample pretreatment, long analysis time, and large consumption of chemicals, thereby generating high amounts of waste. Electroanalytical methods commonly have some advantages over chromatographic methods, such as lower consumption of chemicals, shorter analysis times, and lower cost of instrumentation.
A square-wave voltammetry method for the determination of hydroxychloroquine (HCQ) in pharmaceutical and synthetic urine samples with a cathodically pretreated (CPT) boron-doped diamond (BDD) electrode was successfully developed. Using cyclic voltammetry, the HCQ oxidation was shown to be a one-electron diffusion-controlled process. The obtained SWV analytical curve (I_pa/μA = 0.033 + 1.24 [HCQ/(μmol L⁻¹)]) for HCQ determination (using 0.1 mol L⁻¹ H₂SO₄ as supporting electrolyte) presented a linear response from 0.1 to 1.9 μmol L⁻¹, with a detection limit of 0.06 μmol L⁻¹, the best value attained yet with an unmodified electrode. The proposed method was successfully applied in the determination of HCQ in pharmaceutical (tablets) samples, with results similar at a 95% confidence level to those obtained using a reference spectrophotometric method. Additionally, adequate recovery results were obtained for the determination of HCQ in doped synthetic urine samples. The novel proposed method is inexpensive and fast, with no need of sample pretreatment.
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Determination of the stereoisomers of hydroxychloroquine and its major metabolites in plasma and urine following a single oral administration of racemic hydroxychloroquine

Semin Arthritis Rheum

Clin Rheum Dis