title: Development and validation of a dried blood spot LC-MS/MS assay to quantify ranitidine in paediatric samples.
abstract: A novel approach has been developed to determine ranitidine in paediatric samples using dried blood spots (DBS) on Guthrie cards (Whatman 903). A selective and sensitive HPLC-MS/MS assay has been developed and validated using small volumes of blood (30 μl). A 6 mm disc was punched from each DBS and extracted with methanolic solution of the internal standard (IS) nizatidine. This was further subjected to solid phase extraction (SPE), followed by reversed phase HPLC separation, using a XBridge™ C18 column and mobile phase 10 mM ammonium acetate/methanol (98:2 v/v) with a flow rate of 0.3 mL/min. This was combined with multiple reaction monitoring (MRM) mass detection using electrospray ionisation (ESI). The calibration curve for ranitidine was found linear over the range 10-500 ng/mL (r=0.996). The limit of quantification (LOQ) of the method was validated at 10 ng/mL. Accuracy and precision values for within and between days were <20% at the LOQ and <15% at all other concentrations. The validated DBS method was successfully applied to a clinical study employing 81 samples from 36 paediatric patients.
authors: Clinical and Practice Research Group, School of Pharmacy, Queen's University Belfast, 97, Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom. s.yakkundi@qub.ac.uk
authors: Shirish
authors: S
authors: Yakkundi
authors: Jeff
authors: J
authors: Millership
authors: Paul
authors: P
authors: Collier
authors: Michael D
authors: MD
authors: Shields
authors: James
authors: J
authors: McElnay
mesh_terms: D002648:Child; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006635:Histamine H2 Antagonists / Q000097:blood*; D006801:Humans; D057230:Limit of Detection; D011899:Ranitidine / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D006635:Histamine H2 Antagonists; D011899:Ranitidine