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Measurement of ganciclovir concentration in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry.
Clin Chim Acta. 2014 Jan 01; 427:58-64.CC

Abstract

BACKGROUND

Ganciclovir/valganciclovir plays an important role in the treatment and prevention of cytomegalovirus disease after organ transplantation.

MATERIAL AND 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+Show Affiliations

Laboratori Clínic Department, IDIBELL, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address: raulr@bellvitgehospital.cat.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24120353

Citation

Rigo-Bonnin, Raül, et al. "Measurement of Ganciclovir Concentration in Human Plasma By Ultra-performance Liquid Chromatography-tandem Mass Spectrometry." Clinica Chimica Acta; International Journal of Clinical Chemistry, vol. 427, 2014, pp. 58-64.
Rigo-Bonnin R, Padullés A, Corral-Comesaña S, et al. Measurement of ganciclovir concentration in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry. Clin Chim Acta. 2014;427:58-64.
Rigo-Bonnin, R., Padullés, A., Corral-Comesaña, S., Cerezo, G., Grinyó, J. M., Colom, H., Alía-Ramos, P., & Lloberas, N. (2014). Measurement of ganciclovir concentration in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry. Clinica Chimica Acta; International Journal of Clinical Chemistry, 427, 58-64. https://doi.org/10.1016/j.cca.2013.09.049
Rigo-Bonnin R, et al. Measurement of Ganciclovir Concentration in Human Plasma By Ultra-performance Liquid Chromatography-tandem Mass Spectrometry. Clin Chim Acta. 2014 Jan 1;427:58-64. PubMed PMID: 24120353.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Measurement of ganciclovir concentration in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry. AU - Rigo-Bonnin,Raül, AU - Padullés,Ariadna, AU - Corral-Comesaña,Sofía, AU - Cerezo,Gema, AU - Grinyó,Josep Maria, AU - Colom,Helena, AU - Alía-Ramos,Pedro, AU - Lloberas,Núria, Y1 - 2013/10/10/ PY - 2013/03/01/received PY - 2013/08/23/revised PY - 2013/09/30/accepted PY - 2013/10/15/entrez PY - 2013/10/15/pubmed PY - 2015/1/8/medline KW - ACV KW - AUC KW - Acyclovir KW - CLSI KW - CMV KW - CV KW - Clinical and Laboratory Standards Institute KW - Cytomegalovirus KW - EMA KW - ESI KW - European Medicines Agency KW - GCV KW - Ganciclovir KW - HPLC KW - IFCC KW - International Federation of Clinical Chemistry and Laboratory Medicine KW - LLOD KW - LLOQ KW - MRM KW - MS KW - MS/MS KW - QC KW - S/N KW - SOT KW - Therapeutic drug monitoring KW - UPLC KW - UPLC–MS/MS KW - UV KW - VGCV KW - Valganciclovir KW - acyclovir KW - area under the curve KW - coefficient of variation KW - cytomegalovirus KW - electrospray ionization KW - ganciclovir KW - high-performance liquid chromatography KW - lower limit of detection KW - lower limit of quantification KW - m/z KW - mass spectrometer KW - mass-to-charge KW - multiple reaction monitoring KW - quality control KW - signal-to-noise KW - solid organ transplant KW - tandem mass spectrometry KW - ultra-performance liquid chromatography KW - ultraviolet KW - valganciclovir SP - 58 EP - 64 JF - Clinica chimica acta; international journal of clinical chemistry JO - Clin Chim Acta VL - 427 N2 - BACKGROUND: Ganciclovir/valganciclovir plays an important role in the treatment and prevention of cytomegalovirus disease after organ transplantation. MATERIAL AND 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. SN - 1873-3492 UR - https://www.unboundmedicine.com/medline/citation/24120353/Measurement_of_ganciclovir_concentration_in_human_plasma_by_ultra_performance_liquid_chromatography_tandem_mass_spectrometry_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-8981(13)00397-5 DB - PRIME DP - Unbound Medicine ER -