John Takyi-Williams, Abbie D. Leino, Wen Bo, Duxin Sun, Manjunath P. Pai
Purpose: The monitoring of immunosuppression during organ transplantation enables dose optimization and prevent organ rejection. Volumetric absorptive microsampling (VAMS) is a recent device available for sampling and analyzing low blood volume. The present work describes the utilization of VAMS Tasso-M20™ device for the quantification of tacrolimus and mycophenolic acid(MPA) in human whole blood using bead-based impact-assisted extraction procedure. The result indicated that, sampling volume of the VAMS device was accurate, and together with analyte recovery were independent of the blood hematocrit (HCT). The overall assay was precise and accurate
Krishani K. Rajanayake, Yudong Song, Miao He, Bo Wen, Manjunath Pai, Duxin Sun
Purpose: Here, we successfully demonstrated the application of AP-MALDI (MassTech) coupled to Orbitrap IDX (Thermo) system for localization of small molecular drugs in different mouse tissues. Different instrument parameters and matrices were tested and optimized to achieve the best conditions for the detection of Paclitaxel (PTX), IPI-549, and Avapritinib.
Lu Wang, Miao He, Hongxiang Hu, Bo Wen, Manjunath Pai, Hebao Yuan, Duxin Sun
Purpose: Cyclosporine A (CsA) used as an immunosuppressant agent following organ transplantation and as treatment of several autoimmune diseases. Its clinical use is significantly limited owing to its nephrotoxicity and other serious side effects. In past decades, it’s found that treatment with CsA induced changes to L-carnitine, which is closely tied to components of mitochondrial function. However, the specific effects ofCsA on the carnitine pool, comprised of L-carnitine and the acetylated derivatives, is still not clear. So, a quantitative LC-MS/MS method and a MALDI-MSI method were developed for CsA, L-carnitine and its derivatives. The change of carnitines in mice tissues after treatment with CsA was thus investigated. These results will be helpful for pinpointing the metabolic pathways and toxicity mechanisms of CsA treatment.
Simultaneously Quantitative Profiling of 18 Bile Acids in Human Gastrointestinal Fluid by a Rapid UPLC-MSMS Assay
Ruiting Li, Bo Wen, Praveen Kumar, Amit Pai and Duxin Sun
Purpose: Bile acids (BAs) profiling is increasingly recognized as a useful diagnostic tool to characterize various forms of liver disease as well as genetic conditions that impact BAs metabolism. This BAs characterization has occurred primarily in serum but intraluminal human GI tract have not been well characterized. We developed an ultra pressure liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method to simultaneously quantify 18 BAs in human GI fluid from four different regions (stomach, duodenum, jejunum and ileum) to reveal the BAs homeostasis in human GI tract under physiological situations.
Distinct Pharmacokinetics and Tissue Distribution Study of Four Structure Similar Epidermal Growth Factor Receptor Inhibitors Using Quantitation LC-MSMS
Lu Wang, Miao He, Huixia Zhang, Manjunath Pai, Bo Wen, Hebao Yuan, Duxin Sun
Purpose: Gefitinib Erlotinib Lapatinib and Vandetanib are all epidermal growth factor receptor (inhibitors They have similar target and similar quinazoline based chemical structure, while they are used very differently in clinical, such as Gefitinib for lung cancer, Erlotinib for lung and pancreas cancer, Lapatinib for breast cancer and Vandetanib for thyroid cancer This study aimed to investigate the distinct pharmacokinetics (and tissue distribution of these four EGFR inhibitors, whichmay translated into the difference in their clinical usage and their adverse effects.
Bo Wen, Hebao Yuan, Lipeng Dai, Krishani Rajanayake, Miao He, Manjunath Pai, Duxin Sun
Purpose: In drug discovery and development, it is important to understand the biodistribution and accumulation of drugs in tissue since drug efficacy strongly depends on the presence of the drug substance at the target site. MALDI mass spectrometry imaging (MSI) has become a powerful tool for the detection and localization of drugs. The combination of MALDI and ion mobility enable the mass and time selected ion images. Here, we report a specific approach to explore the heterogeneous distribution of paclitaxel (PTX) in solid tumor by MALDI-ion mobility MSI using commercially available TiO2 nanoparticles as the matrix. Four clinically approved paclitaxel nanoparticle formulations were studied. In addition, the MSI results were coregeistered with immunohistochemical staining to evaluate the location of drug on tissue.
Acknowledgements: This research wassupported by the National Cancer Institute of the National Institutes of Health under award number P30CA046592."
A Sensitive and Selective LC-MSMS Approach for Simultaneous Determination of 18 Cytotoxic Anticancer Agents in Human Plasma for the Assessment of Occupational Safety
Ting Zhao,1 Bo Wen,1 Huixia Zhang,1 Ruijuan Luo,1 Siwei Li,1 Miao He,1 Kari Mendelsohn-Victor,2 Christopher R. Friese,2 Duxin Sun.1
Purpose: In the last decade, the use of cytotoxic drugs has increased considerably in cancer therapy. Besides curative effects, the cytotoxic agents have potential carcinogenic and mutagenic effects on human. There is an increased concern of the occupational safety and health risks of the nurses in ambulatory oncology settings due to their frequent exposure to a large amount of the cytotoxic anticancer drugs. In order to measure the drug level of 18 frequently used hazardous anticancer agents in the nurse plasma samples and assess the occupational exposure of the ambulatory oncology nurses, we developed a fast, sensitive and reproducible liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of the 18 anticancer drugs in human plasma
Acknowledgements: This research was supported by National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention R01 OH 010582–01.
Regional In Vivo Dissolution of Immediate Release Ibuprofen in Human Gastrointestinal Tract and Its Relationship to Luminal pH, GI Motility, and Systemic Absorption
Mark J. Koenigsknecht1, Jason R. Baker,2 Ann F. Fioritto1, Yasuhiro Tsume1, Bo Wen,1 Ting Zhao1, Joseph Dickens3, Alex Yu1, Jeffery Wysocki2, Kerby Shedden3, Barry Bleske1, Allen Lee2, William L. Hasler2, Gordon L. Amidon1, Duxin Sun1
Purpose: Extensive information on in vitro drug dissolution is required for approval of new drugs, but the ability to measure in vivo dissolution and bioavailability is limited. Drug dose, dissolution, gastric emptying, gastrointestinal (GI) motility, solubility, and intestinal content influence systemic drug absorption. Regional GI tract in vivo drug dissolution must be better understood to refine in vitro methodologies to predict drug bioavailability. We aimed to quantify plasma and GI luminal concentrations of the highly absorbable drug ibuprofen in different regions of the stomach and small bowel in relation to fasting vs. fed status and to luminal pH, GI motility, and fluid dynamics using a novel multi-lumen aspiration catheter in healthy humans.
Acknowledgements: This research was supported by FDA grant HHSF223201310144C
