Quantification of intact carboplatin in human plasma ultrafitrates using hydrophilic interaction liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.
Carboplatin is a platinum agent that is used for treatment of non-small-cell lung cancer and ovarian cancer. A sensitive and selective analytical method for the quantification of carboplatin in human plasma ultrafiltrates using liquid chromatography-tandem mass spectrometry was developed. Human plasma ultrafiltrates were precipitated by acetonitrile containing carboplatin-d4 as an internal standard and were further diluted with acetonitrile. Chromatographic separation was performed on a Accucore HILIC (50mm×2.1mm i.d., 2.6μm) column using mobile phase (acetonitrile-water-acetic acid=90:10:0.1, v/v/v) at the flow rate of 0.2mL/min. Detection was performed on electrospray ionization triple quadrupole tandem mass spectrometer using low-energy collision induced dissociation (CID-MS/MS) analysis operating in the selected reaction monitoring (SRM) scan mode. The lower limit of quantification for carboplatin was 0.025μg/mL. This method covered a linearity range of 0.025-50μg/mL. The intra-day precision and inter-day precision (R.S.D.) ranged from 1.5 to 4.3%, and the accuracy (R.E.) was within ±2.9%. The present method was applied to a clinical pharmacokinetic study of carboplatin in a cancer patient.
Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Hajime
H
Ito
Hiroaki
H
Yamaguchi
Asuka
A
Fujikawa
Narumi
N
Shiida
Nobuaki
N
Tanaka
Jiro
J
Ogura
Masaki
M
Kobayashi
Takehiro
T
Yamada
Nariyasu
N
Mano
Ken
K
Iseki
D016190:Carboplatin / Q000097:blood* / Q000302:isolation & purification / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D016014:Linear Models; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014462:Ultrafiltration
D016190:Carboplatin