Send to

Choose Destination
See comment in PubMed Commons below
J Lipid Res. 2014 Jul;55(7):1537-48. doi: 10.1194/jlr.D050278. Epub 2014 May 27.

Development and validation of sensitive LC-MS/MS assays for quantification of HP-β-CD in human plasma and CSF.

Author information

Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO.
Janssen Research and Development, Springhouse, PA.
Beerse, Belgium, Janssen Research and Development, Springhouse, PA.
Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD.
Nursing Department, National Institutes of Health, Bethesda, MD.


2-Hydroxypropyl-β-cyclodextrin (HP-β-CD), a widely used excipient for drug formulation, has emerged as an investigational new drug for the treatment of Niemann-Pick type C1 (NPC1) disease, a neurodegenerative cholesterol storage disorder. Development of a sensitive quantitative LC-MS/MS assay to monitor the pharmacokinetics (PKs) of HP-β-CD required for clinical trials has been challenging owing to the dispersity of the HP-β-CD. To support a phase 1 clinical trial for ICV delivery of HP-β-CD in NPC1 patients, novel methods for quantification of HP-β-CD in human plasma and cerebrospinal fluid (CSF) using LC-MS/MS were developed and validated: a 2D-LC-in-source fragmentation-MS/MS (2D-LC-IF-MS/MS) assay and a reversed phase ultra performance LC-MS/MS (RP-UPLC-MS/MS) assay. In both assays, protein precipitation and "dilute and shoot" procedures were used to process plasma and CSF, respectively. The assays were fully validated and in close agreement, and allowed determination of PK parameters for HP-β-CD. The LC-MS/MS methods are ∼100-fold more sensitive than the current HPLC assay, and were successfully employed to analyze HP-β-CD in human plasma and CSF samples to support the phase 1 clinical trial of HP-β-CD in NPC1 patients.


2-hydroxypropyl-β-cyclodextrin; Niemann-Pick C; cerebrospinal fluid; in-source fragmentation; liquid chromatography-tandem mass spectrometry; two-dimensional liquid chromatography; ultra performance liquid chromatography

PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center