title: Laser diode thermal desorption-positive mode atmospheric pressure chemical ionization tandem mass spectrometry for the ultra-fast quantification of a pharmaceutical compound in human plasma.
abstract: An ultra-fast, reliable and sensitive analytical method enabling high-throughput quantitative analysis of pharmaceutical compounds in human plasma is described. The quantitative work was performed on one of our compound currently under clinical trial by employing a deuterated internal standard (IS). Plasma samples were treated on solid phase micro-extraction (SPME) plates prior their analysis by laser diode thermal desorption and atmospheric pressure chemical ionization coupled to tandem mass spectrometry (LDTD/APCI-MS/MS) in positive mode. The sample analysis run time was 10s as compared to the 7 min obtained for the validated LC-MS/MS method. The limit of quantification (LOQ) of the method was estimated at 1 ng/mL. The calibration graphs were linear with a regression coefficient R(2) > 0.997. The data of the partial validation show that LDTD/APCI-MS/MS assay was highly reproducible and selective. In addition, the deviations for intra and inter assay accuracy and precision data were within 15% at all quality control levels. The LDTD/APCI-MS/MS method was successfully applied to the analysis of clinical samples and the data obtained were consistent with those found with a validated LC-MS/MS assay. This work demonstrates that LDTD/APCI-MS/MS could be used for the ultra-fast and reliable quantitative analysis of pharmaceutical compounds in human plasma without using the separation step commonly associated with the LC-MS/MS assay.
authors.affiliation: Novartis Pharma AG, DMPK/Bioanalytics, CH-4056 Basel, Switzerland. olivier.heudi@novartis.com
authors.forename: Olivier
authors.initials: O
authors.lastname: Heudi
authors.forename: Samuel
authors.initials: S
authors.lastname: Barteau
authors.forename: Pierre
authors.initials: P
authors.lastname: Picard
authors.forename: Patrice
authors.initials: P
authors.lastname: Tremblay
authors.forename: Franck
authors.initials: F
authors.lastname: Picard
authors.forename: Olivier
authors.initials: O
authors.lastname: Kretz
mesh_terms: D002138:Calibration; D004341:Drug Evaluation / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D006801:Humans; D057230:Limit of Detection; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000097:blood*; D012015:Reference Standards; D052617:Solid Phase Microextraction; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations