Rapid Interference-free Analysis of β-Lapachone in Clinical Samples Using Liquid Chromatography–Mass Spectrometry for a Pharmacokinetic Study in Humans

A rapid analytical method developed for the analysis of β-lapachone in in vitro samples could not be directly applied to the analysis of clinical samples because of interference from unknown substances. Here, we developed and validated a rapid interference-free analytical method to accurately determ...

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Bibliographic Details
Published in:Analytical Sciences 2021/08/10, Vol.37(8), pp.1105-1110
Main Authors: KIM, Bo Kyung, GWON, Mi-Ri, KANG, Woo Youl, LEE, In-Kyu, LEE, Hae Won, SEONG, Sook Jin, CHO, Seungil, YOON, Young-Ran
Format: Article
Language:English
Subjects:
Analytical Chemistry
Chemistry
Chromatography, High Pressure Liquid
Chromatography, Liquid
Humans
Interference
LC-MS/MS
MB12066
Naphthoquinones
Original Paper
pharmacokinetic study
Reproducibility of Results
Spectrometry, Mass, Electrospray Ionization
Tandem Mass Spectrometry
β-lapachone
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Summary:A rapid analytical method developed for the analysis of β-lapachone in in vitro samples could not be directly applied to the analysis of clinical samples because of interference from unknown substances. Here, we developed and validated a rapid interference-free analytical method to accurately determine β-lapachone levels in human plasma using liquid chromatography–tandem mass spectrometry. First, we achieved the baseline-separation of β-lapachone from any interfering substances within a total run time of 4 min by adjusting the eluent strength of the mobile phase. Second, precursor-ion scanning revealed the identity of the interfering substances. Sulfonate- or glucuronide-conjugated metabolites were converted to β-lapachone in an electrospray ion source, causing interference. In a method validation study, calibration curves for β-lapachone in human plasma were linear over a concentration range from 0.5 to 200 ng/mL (r > 0.999), and the lower limit of quantification was 0.5 ng/mL. The other validation parameters, including intra- and interday accuracy and precision, were acceptable with a coefficient of variation less than 10% (n = 5). The validated analytical method was successfully applied to a pharmacokinetic study of a single, oral dose of 100 mg MB12066 (a clinical form of β-lapachone) in healthy volunteers.
ISSN:0910-6340
1348-2246
DOI:10.2116/analsci.20P385