TY - JOUR
T1 - Development and validation of sensitive LC-MS/MS assays for quantifi cation of HP- β -CD in human plasma and CSF
AU - Jiang, Hui
AU - Sidhu, Rohini
AU - Fujiwara, Hideji
AU - Meulder, Marc De
AU - De Vries, Ronald
AU - Gong, Yong
AU - Kao, Mark
AU - Porter, Forbes D.
AU - Yanjanin, Nicole M.
AU - Carillo-Carasco, Nuria
AU - Xu, Xin
AU - Ottinger, Elizabeth
AU - Woolery, Myra
AU - Ory, Daniel S.
AU - Jiang, Xuntian
PY - 2014/7
Y1 - 2014/7
N2 - 2-Hydroxypropyl- cyclodextrin (HP- -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- CD required for clinical trials has been challenging owing to the dispersity of the HP- -CD. To support a phase 1 clinical trial for ICV delivery of HP- -CD in NPC1 patients, novel methods for quantification of HP- CD in human plasma and cerebrospinal fl uid (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- CD. The LC-MS/MS methods are 100- fold more sensitive than the current HPLC assay, and were successfully employed to analyze HP- CD in human plasma and CSF samples to support the phase 1 clinical trial of HP- CD in NPC1 patients. -Jiang, H., R. Sidhu, H. Fujiwara, M. De Meulder, R. de Vries, Y. Gong, M. Kao, F. D. Porter, N. M. Yanjanin, N. Carillo-Carasco, X. Xu, E. Ottinger, M. Woolery, D. S. Ory, and X. Jiang. Development and validation of sensitive LC-MS/MS assays for quantifi cation of HP- CD in human plasma and CSF. J. Lipid Res. 2014. 55: 1537 - 1548 .
AB - 2-Hydroxypropyl- cyclodextrin (HP- -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- CD required for clinical trials has been challenging owing to the dispersity of the HP- -CD. To support a phase 1 clinical trial for ICV delivery of HP- -CD in NPC1 patients, novel methods for quantification of HP- CD in human plasma and cerebrospinal fl uid (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- CD. The LC-MS/MS methods are 100- fold more sensitive than the current HPLC assay, and were successfully employed to analyze HP- CD in human plasma and CSF samples to support the phase 1 clinical trial of HP- CD in NPC1 patients. -Jiang, H., R. Sidhu, H. Fujiwara, M. De Meulder, R. de Vries, Y. Gong, M. Kao, F. D. Porter, N. M. Yanjanin, N. Carillo-Carasco, X. Xu, E. Ottinger, M. Woolery, D. S. Ory, and X. Jiang. Development and validation of sensitive LC-MS/MS assays for quantifi cation of HP- CD in human plasma and CSF. J. Lipid Res. 2014. 55: 1537 - 1548 .
KW - 2-hydroxypropyl- - -cyclodextrin
KW - Cerebrospinal fl uid
KW - In-source fragmentation
KW - Liquid chromatography-tandem mass spectrometry
KW - Niemann-Pick C
KW - Two-dimensional liquid chromatography
KW - Ultra performance liquid chromatography
UR - http://www.scopus.com/inward/record.url?scp=84903999212&partnerID=8YFLogxK
U2 - 10.1194/jlr.D050278
DO - 10.1194/jlr.D050278
M3 - Article
C2 - 24868096
AN - SCOPUS:84903999212
SN - 0022-2275
VL - 55
SP - 1537
EP - 1548
JO - Journal of lipid research
JF - Journal of lipid research
IS - 7
ER -