Development and validation of a clinical HPLC method for the quantification of hydroxychloroquine and its metabolites in whole blood

Ying Qu; Gaelle Noe; Autumn R Breaud; Michel Vidal; William A Clarke; Noel Zahr; Thierry Dervieux; Nathalie Costedoat-Chalumeau; Benoit Blanchet

doi:10.4155/fso.15.24

Development and validation of a clinical HPLC method for the quantification of hydroxychloroquine and its metabolites in whole blood

Future Sci OA. 2015 Nov 1;1(3):FSO26. doi: 10.4155/fso.15.24. eCollection 2015 Nov.

Authors

Ying Qu¹, Gaelle Noe², Autumn R Breaud³, Michel Vidal⁴, William A Clarke³, Noel Zahr⁵, Thierry Dervieux¹, Nathalie Costedoat-Chalumeau⁶, Benoit Blanchet²

Affiliations

¹ Research & Development, Exagen Diagnostic, 1261 Liberty Way, Vista, CA 92081, USA; Research & Development, Exagen Diagnostic, 1261 Liberty Way, Vista, CA 92081, USA.
² UF de Pharmacocinétique et Pharmacochimie, Hôpital Cochin, APHP, 27 Rue Faubourg St Jacques, 75014 Paris, France; UF de Pharmacocinétique et Pharmacochimie, Hôpital Cochin, APHP, 27 Rue Faubourg St Jacques, 75014 Paris, France.
³ Clinical Chemistry, Department of Pathology, The John Hopkins University, Baltimore, MD 21287, USA; Clinical Chemistry, Department of Pathology, The John Hopkins University, Baltimore, MD 21287, USA.
⁴ UF de Pharmacocinétique et Pharmacochimie, Hôpital Cochin, APHP, 27 Rue Faubourg St Jacques, 75014 Paris, France; UMR8638 CNRS, UFR de Pharmacie, Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France; UF de Pharmacocinétique et Pharmacochimie, Hôpital Cochin, APHP, 27 Rue Faubourg St Jacques, 75014 Paris, France; UMR8638 CNRS, UFR de Pharmacie, Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France.
⁵ Laboratoire de Pharmacologie, Groupe Hospitalier Pitié-Salpêtrière, APHP, 47-83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France; Laboratoire de Pharmacologie, Groupe Hospitalier Pitié-Salpêtrière, APHP, 47-83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.
⁶ Université Paris-Descartes, Paris, France; AP-HP, Hôpital Cochin, Centre de Référence Maladies Auto-Immunes et Systémiques Rares, Service de Médecine Interne, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France; Université Paris-Descartes, Paris, France; AP-HP, Hôpital Cochin, Centre de Référence Maladies Auto-Immunes et Systémiques Rares, Service de Médecine Interne, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France.

Abstract

Background: Therapeutic drug monitoring for hydroxychloroquine (HCQ) has been suggested to assess nonadherence and optimize treatment efficacy in systemic lupus erythematosus patients.

Materials & methods: After protein precipitation, HCQ and its metabolites, desethylhydroxychloroquine and desethylchloroquine were separated on a phenyl column and monitored by fluorescence detection. The method was linear from 50 to 4000 ng/ml for HCQ. The intra-day and inter-day precision of HCQ, desethylhydroxychloroquine and desethylchloroquine ranged from 4.3 to 10.3%. LLOQ was 50 ng/ml for HCQ.

Conclusion: The method is very practical and was applied to routinely monitor the steady state whole blood exposure of HCQ and its metabolites in systemic lupus erythematosus patients. It well correlated with our LC-MS/MS and another HPLC method.

Keywords: HPLC; LC–MS/MS; clinical drug monitoring; desethylchloroquine; desethylhydroxychloroquine; drug monitoring; fluorescence detection; hydroxychloroquine; systemic lupus erythematosus; whole blood.