Journal
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
Volume 1072, Issue -, Pages 320-327Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jchromb.2017.11.026
Keywords
LC-MS/MS; Hydroxychloroquine; Desethyl hydroxychloroquine; Chemosensitization; Malaria; Pharmacokinetics
Funding
- State of Nebraska through the Pediatric Cancer Research Group
- University of Nebraska Medical Center
- Fred & Pamela Buffett Cancer Center Support Grant from the National Cancer Institute [P30 CA036727]
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Hydroxychloroquine (HCQ) has been shown to disrupt autophagy and sensitize cancer cells to radiation and chemotherapeutic agents. However, the optimal delivery method, dose, and tumor concentrations required for these effects are not known. This is in part due to a lack of sensitive and reproducible analytical methods for HCQ quantitation in small animals. As such, we developed and validated a selective and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues. The chromatographic separation and detection of analytes were achieved on a reversed phase Thermo Aquasil C-18 (50 x 4.6 mm, 3 mu) column, with gradient elution using 0.2% formic acid and 0.1% formic acid in methanol as mobile phase at a flow rate of 0.5 mL/min. Simple protein precipitation was utilized for extraction of analytes from the desired matrix. Analyies were separated and quantitated using MS/MS with an electrospray ionization source in positive multiple reaction monitoring (MRM) mode. The MS/MS response was linear over the concentration range from 1 to 2000 ng/mL for all analytes with a correlation coefficient (R-2) of 0.998 or better. The within- and between-day precision (relative standard deviation, % RED) and accuracy were within the acceptable limits per FDA guidelines. The validated method was successfully applied to a preclinical pharmacokinetic mouse study involving low volume blood and tissue samples for hydroxychloroquine and metabolites.
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