Functionalized graphene oxide tablets for sample preparation of drugs in biological fluids: Extraction of ritonavir, a HIV protease inhibitor, from human saliva and plasma using LC-MS/MS

In this work, graphene oxide-based tablets (GO-Tabs) were prepared by applying a thin layer of functionalized GO on a polyethylene substrate. The GO was functionalized with amine groups (-NH2) by polyethylene glycol)bis(3-aminopropyl) terminated (GO-NH2-PEG-NH2). The functionalized GO-Tabs were used for the extraction of ritonavir (RTV) in human saliva samples. RTV in plasma and saliva samples was analyzed using LC-MS/MS. Gradient LC system with MS/MS in the positive-ion mode [electrospray ionization (ESI+)] was used. The transitions m/z 721 -> 269.0 and m/z 614 -> 421 were used for RTV and the internal standard indinavir, respectively. This study determined the human immunodeficiency virus protease inhibitor RTV in human saliva samples using functionalized GO-Tab and LC-MS/MS, and the method was validated. The standard calibration curve for plasma and saliva samples was constructed from 5.0 to 2000 nmol L-1. The limit of detection was 0.1 nmol L-1, and the limit of quantification was 5.0 nmol L-1 in both plasma and saliva matrices. The intra- and inter-assay precision values were found to be between 1.5 and 5.8%, and the accuracy values ranged from 88.0 to 108% utilizing saliva and plasma samples. The extraction recovery was more than 80%, and the presented functionalized GO-Tabs could be reused for more than 10 extractions without deterioration in recovery.