title: Rapid assay of topiramate in dried blood spots by a new liquid chromatography-tandem mass spectrometric method.
abstract: Topiramate (TPM) is a new antiepiletic drug with efficacy in several types of seizures. Therapeutic drug monitoring of TPM is essential for effective patient management. The aim of this study was to evaluate the use of dried blood spot (DBS) specimens to determinate the TPM levels during the treatment. Advantages of DBS include short collection time, low invasiveness, ease and low cost of sample collection, transport and storage. Performance comparison between this method and the commercially available fluorescence-polarization immunoassay (FPIA) was made. The analysis was performed in selected reaction monitoring (SRM) mode. The calibration curve in matrix using D(12)-topiramate was linear in the concentration range of 0.0166-1.66mg/L (0.5-50mg/L in DBS) of topiramate with correlation coefficient value of 0.9985. In the concentration range of 0.5-50mg/L, the coefficients of variation in DBS were in the range 2.13-11.85% and the accuracy ranged from 93.93% to 110.67%. There was no significant differences between the concentrations (ranging 0.5-50mg/L) measured both FPIA on venous samples and LC-MS/MS assay on simultaneous DBS samples. The sensitivity and specificity of tandem mass spectrometry allow now high throughput topiramate analysis (the improvement was three times in comparison with FPIA). This new assay has favourable characteristics being highly precise and accurate. FPIA also proved to be precise and accurate, but is not always suitable for the sample collection in neonates in whom obtaining larger blood samples is not convenient or possible.
authors.affiliation: Mass Spectrometry Laboratory, Clinic of Pediatric Neurology, A Meyer Children's Hospital, Florence, Italy. g.lamarca@meyer.it
authors.forename: Giancarlo
authors.initials: G
authors.lastname: la Marca
authors.forename: Sabrina
authors.initials: S
authors.lastname: Malvagia
authors.forename: Luca
authors.initials: L
authors.lastname: Filippi
authors.forename: Patrizio
authors.initials: P
authors.lastname: Fiorini
authors.forename: Marzia
authors.initials: M
authors.lastname: Innocenti
authors.forename: Francesca
authors.initials: F
authors.lastname: Luceri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pieraccini
authors.forename: Gloriano
authors.initials: G
authors.lastname: Moneti
authors.forename: Simona
authors.initials: S
authors.lastname: Francese
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Dani
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
mesh_terms: D000927:Anticonvulsants / Q000032:analysis* / Q000737:chemistry; D001681:Biological Assay / Q000379:methods; D001800:Blood Specimen Collection / Q000379:methods*; D002138:Calibration; D016022:Case-Control Studies; D002853:Chromatography, Liquid / Q000379:methods; D003890:Desiccation / Q000379:methods*; D004827:Epilepsy / Q000097:blood; D005454:Fluorescence Polarization / Q000379:methods; D005632:Fructose / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D006801:Humans; D007118:Immunoassay; D015394:Molecular Structure; D012015:Reference Standards; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose