Simon Zhou, Krishani Kumari Rajanayake, Miao He, Bo Wen, Ankhbayar Lkhagva, Ernie Yap, Duxin Sun, Jennifer Cross, Kory Engelke, Robert B Huizinga
Purpose:The calcineurin inhibitors (CNIs) cyclosporine A (CSA) and tacrolimus (TAC) were revolutionary immunosuppressants when first introduced for solid organ transplantation in the 1980. Voclosporin, a novel CNI, recently became the first oral therapy approved in the United States and Europe for the treatment of active lupus nephritis (LN) in adult patients based on positive results from Phase 2 and 3 clinical trials2. Unlike CSA and TAC, voclosporin has a consistent pharmacokinetic and pharmacodynamic profile, eliminating the need for therapeutic drug monitoring. In clinical trials of LN, voclosporin was associated with a favorable lipid and glucose profile and no drug-drug interaction with mycophenolate mofetil (MMF).
John Takyi-Williams1, Ruiting Li1,  Amanda Bwint2, Bo Wen1, Duxin Sun1, Marc Scheetz3, Kevin J. Downes2, Athena F. Zuppa2, Manjunath P. Pai1
Purpose: Improving antimicrobial drug dosing in pediatric patients requires high quality multicenter  pharmacokinetics and pharmacodynamics (PK/PD) studies. Robust analytical methods that can reduce blood sample volume, enable central laboratory transfer and measure multiple analytes can help overcome barriers associated with these studies.  Volumetric absorptive microsampling (VAMS) is a recent device available for sampling and analyzing low blood volume and enable ease of transportation.

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.


PDF iconSimultaneously 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.

PDF icon 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."  

PDF iconA 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





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Thursday, November 3, 2016
Thursday, November 3, 2016