title: Measurement of ganciclovir concentration in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry.
abstract: BACKGROUND
  Ganciclovir/valganciclovir plays an important role in the treatment and prevention of cytomegalovirus disease after organ transplantation.
  
  
  METHODS
  We developed and validated a simple chromatographic method by ultra-performance liquid chromatography tandem mass spectrometry to measure plasma concentration of ganciclovir in human plasma. Chromatographic separation was achieved using an Acquity(®) UPLC(®) BEH™ (2.1×50mm id, 1.7μm) reverse-phase C18 column, with a water/methanol linear gradient containing ammonium acetate/formic acid at a 0.4mL/min flow rate. Ganciclovir and its internal standard (acyclovir) were detected by electrospray ionization mass spectrometry in positive ion multiple reaction monitoring mode.
  
  
  RESULTS
  The limit of detection and quantification were 0.03 and 0.06mg/L, respectively, and linearity was observed between 0.06 and 30.0mg/L. Intra-day and day-to-day coefficients of variation and relative biases ranged from 3.6 to 5.4%, 4.2 to 6.2%, -2.6 to -1.1% and -4.0 to -2.8%, respectively. Recovery values were greater than 81.9%. Evaluation of the matrix effect showed ion suppression for ganciclovir and acyclovir. No carry-over was observed.
  
  
  CONCLUSIONS
  The validated method is useful for both therapeutic drug monitoring and pharmacokinetic studies. It could be applied to the daily clinical laboratory practice to measure the concentration of ganciclovir in human plasma.
authors.affiliation: Laboratori Clínic Department, IDIBELL, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address: raulr@bellvitgehospital.cat.
authors.forename: Raül
authors.initials: R
authors.lastname: Rigo-Bonnin
authors.forename: Ariadna
authors.initials: A
authors.lastname: Padullés
authors.forename: Sofía
authors.initials: S
authors.lastname: Corral-Comesaña
authors.forename: Gema
authors.initials: G
authors.lastname: Cerezo
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Grinyó
authors.forename: Helena
authors.initials: H
authors.lastname: Colom
authors.forename: Pedro
authors.initials: P
authors.lastname: Alía-Ramos
authors.forename: Núria
authors.initials: N
authors.lastname: Lloberas
mesh_terms: D002851:Chromatography, High Pressure Liquid; D015774:Ganciclovir / Q000097:blood*; D006801:Humans; D053719:Tandem Mass Spectrometry
chemical_list: D015774:Ganciclovir
keywords: ACV; AUC; Acyclovir; CLSI; CMV; CV; Clinical and Laboratory Standards Institute; Cytomegalovirus; EMA; ESI; European Medicines Agency; GCV; Ganciclovir; HPLC; IFCC; International Federation of Clinical Chemistry and Laboratory Medicine; LLOD; LLOQ; MRM; MS; MS/MS; QC; S/N; SOT; Therapeutic drug monitoring; UPLC; UPLC–MS/MS; UV; VGCV; Valganciclovir; acyclovir; area under the curve; coefficient of variation; cytomegalovirus; electrospray ionization; ganciclovir; high-performance liquid chromatography; lower limit of detection; lower limit of quantification; m/z; mass spectrometer; mass-to-charge; multiple reaction monitoring; quality control; signal-to-noise; solid organ transplant; tandem mass spectrometry; ultra-performance liquid chromatography; ultraviolet; valganciclovir