Portfolio of Our Published Work

We developed and validated novel analytical methods, and analyzed specimens in support of the following:



Population Pharmacokinetics of Doxycycline in Children

Doxycycline concentrations in plasma were quantified using a validated high performance liquid chromatography (HPLC)–tandem mass spectrometry (MS-MS) assay.   The lower limit of quantification for doxycycline was 50 ng/mL.

Thompson EJ, Wu H, Melloni C, et al. Antimicrob Agents Chemother. 2019;63(12):e01508-19. doi:10.1128/AAC.01508-19


Population Pharmacokinetics and Safety of Piperacillin-Tazobactam Extended Infusions in Infants and Children

Piperacillin and tazobactam concentrations were quantified using validated liquid chromatography-tandem mass spectrometry assays.   The lower limit of quantification (LLOQ) was 0.1 mg/L for both piperacillin and tazobactam.

Thibault C, Lavigne J, Litalien C, Kassir N, Théorêt Y, Autmizguine J. Antimicrob Agents Chemother. 2019;63(11):e01260-19. Published 2019 Oct 22. doi:10.1128/AAC.01260-19


Rifampin Pharmacokinetics and Safety in Preterm and Term Infants

Rifampin concentrations were quantified using a validated liquid chromatography-tandem spectrometry assay.   The validation range for the assay was 0.05 to 50 μg/mL.

Smith PB, Cotten CM, Hudak ML, et al. Antimicrob Agents Chemother. 2019;63(6):e00284-19. Published 2019 May 24. doi:10.1128/AAC.00284-19


Pharmacokinetics of Ticarcillin–clavulanate in Premature Infants

Total ticarcillin concentrations in plasma were quantified using a validated HPLC/MS/MS assay.   The lower limit of quantification was 500 ng/mL.

Watt KM, Hornik CP, Balevic SJ, et al. Br J Clin Pharmacol. 2019;85(5):1021-1027. doi:10.1111/bcp.13882


The Fungal Cyp51-Specific Inhibitor VT-1598 Demonstrates In Vitro and In Vivo Activity against Candida auris

VT-1598 concentrations were determined by liquid chromatography-tandem mass spectrometry (LC/MS-MS).

Wiederhold NP, Lockhart SR, Najvar LK, et al. Antimicrob Agents Chemother. 2019;63(3):e02233-18. Published 2019 Feb 26. doi:10.1128/AAC.02233-18


A Population-Based Pharmacokinetic Model Approach to Pantoprazole Dosing for Obese Children and Adolescents

Pantoprazole and pantoprazole-sulfone concentrations in plasma were quantified using a validated high-performance liquid chromatography tandem mass spectrometry (HPLC/MS-MS) assay.   The lower limit of quantification for both pantoprazole and pantoprazole-sulfone were 10 ng/mL.

Shakhnovich V, Brian Smith P, Guptill JT, et al. Paediatr Drugs. 2018;20(5):483-495. doi:10.1007/s40272-018-0305-1


Population Pharmacokinetics and Exploratory Exposure-Response Relationships of Diazepam in Children Treated for Status Epilepticus

Diazepam concentrations were quantified using a validated liquid chromatography-tandem spectrometry assay.   The lower limit of quantification was 1 ng/mL.

Ku LC, Hornik CP, Beechinor RJ, et al. CPT Pharmacometrics Syst Pharmacol. 2018;7(11):718-727. doi:10.1002/psp4.12349


VT-1598 inhibits the in vitro growth of mucosal Candida strains and protects against fluconazole-susceptible and -resistant oral candidiasis in IL-17 signalling-deficient mice

VT-1598 levels were determined in tongue homogenates and plasma using LC-MS/MS.

Break TJ, Desai JV, Healey KR, et al. J Antimicrob Chemother. 2018;73(8):2089-2094. doi:10.1093/jac/dky170


The Novel Fungal Cyp51 Inhibitor VT-1598 Is Efficacious in Experimental Models of Central Nervous System Coccidioidomycosis Caused by Coccidioides posadasii and Coccidioides immitis

Plasma concentrations of VT-1598 and the positive control VT-1161 were determined by liquid chromatography/tandem mass spectrometry.

Wiederhold NP, Shubitz LF, Najvar LK, et al. Antimicrob Agents Chemother. 2018;62(4):e02258-17. Published 2018 Mar 27. doi:10.1128/AAC.02258-17


A Pharmacokinetic Model for Amiodarone in Infants Developed from an Opportunistic Sampling Trial and Published Literature Data

Amiodarone plasma concentrations were quantified using a validated high-performance liquid chromatography tandem-mass spectrometry assay.   The calibration range was between 5–5000 ng/mL using a 10 uL sample volume.

Dallefeld SH, Atz AM, Yogev R, et al. J Pharmacokinet Pharmacodyn. 2018;45(3):419-430. doi:10.1007/s10928-018-9576-y


Obese Children Require Lower Doses of Pantoprazole Than Nonobese Peers to Achieve Equal Systemic Drug Exposures

Pantoprazole and pantoprazole-sulfone concentrations in plasma were quantified using a validated high-performance liquid chromatography tandem mass spectrometry assay.   The lower limit of quantification for both pantoprazole and pantoprazole sulfone were 10 ng/mL.

Shakhnovich V, Smith PB, Guptill JT, et al. J Pediatr. 2018;193:102-108.e1. doi:10.1016/j.jpeds.2017.10.011


Comparative Analysis of Ampicillin Plasma and Dried Blood Spot Pharmacokinetics in Neonates

Ampicillin concentrations were measured using a validated bioanalytical high-pressure liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay.   The validated range of the method for ampicillin based on 10 μLs of human plasma was 0.05 to 50 μg/mL.

Le J, Poindexter B, Sullivan JE, et al. Ther Drug Monit. 2018;40(1):103-108. doi:10.1097/FTD.0000000000000466


Population Pharmacokinetics of Trimethoprim-Sulfamethoxazole in Infants and Children

Trimethoprim (TMP) and Sulfamethoxazole (SMX) concentrations were quantified using validated liquid chromatography-tandem mass spectrometry assays.   The TMP validation range was 25 to 50,000 ng/mL.   The SMX validation range was 250 to 500,000 ng/mL.

Autmizguine J, Melloni C, Hornik CP, et al. Antimicrob Agents Chemother. 2017;62(1):e01813-17. Published 2017 Dec 21. doi:10.1128/AAC.01813-17


Development of a Pediatric Physiologically Based Pharmacokinetic Model of Clindamycin Using Opportunistic Pharmacokinetic Data

Clindamycin plasma concentrations were quantified using a validated liquid chromatography-tandem spectrometry (LC-MS/MS) assay.   The validation range for the assay was 50–50,000 ng/mL.

Hornik CP, Wu H, Edginton AN, Watt K, Cohen-Wolkowiez M, Gonzalez D. Clin Pharmacokinet. 2017;56(11):1343-1353. doi:10.1007/s40262-017-0525-5


VT-1161 protects mice against oropharyngeal candidiasis caused by fluconazole-susceptible and -resistant Candida albicans

VT-1161 and VT-1129 concentrations were determined using LC–MS/MS with electrospray ionization.

Break TJ, Desai JV, Natarajan M, et al. J Antimicrob Chemother. 2018;73(1):151-155. doi:10.1093/jac/dkx352


Antifungal Extraction by the Extracorporeal Membrane Oxygenation Circuit

Fluconazole concentrations were measured using HPLC/MS-MS.   The lower limit of quantification (LLOQ) was .01 mg/L with a calibration curve range of .01–10 mg/L.

Watt KM, Cohen-Wolkowiez M, Williams DC, et al. J Extra Corpor Technol. 2017;49(3):150-159.


Prophylactic Treatment with VT-1161 Protects Immunosuppressed Mice from Rhizopus arrhizus var. arrhizus Infection

VT-1161 levels were measured by liquid chromatography-tandem mass spectrometry (LC/MS-MS).

Gebremariam T, Alkhazraji S, Lin L, et al. Antimicrob Agents Chemother. 2017;61(9):e00390-17. Published 2017 Aug 24. doi:10.1128/AAC.00390-17


Population Pharmacokinetics and Exploratory Pharmacodynamics of Lorazepam in Pediatric Status Epilepticus

Plasma lorazepam concentrations were quantified using a validated liquid chromatography-tandem mass spectrometry assay developed by the Pediatric Trials Network (PTN) central laboratory (OpAns, Durham, NC).   Calibration standards ranged from 1 to 500 ng/mL in human plasma.

Gonzalez D, Chamberlain JM, Guptill JT, et al. Clin Pharmacokinet. 2017;56(8):941-951. doi:10.1007/s40262-016-0486-0


Efficacy of the Investigational Antifungal VT-1161 in Treating Naturally Occurring Coccidioidomycosis in Dogs

VT-1161 was extracted from plasma samples and analyzed using high-performance liquid chromatography with tandem mass spectrometry using electrospray ionization.

Shubitz LF, Roy ME, Trinh HT, Hoekstra WJ, Schotzinger RJ, Garvey EP. Antimicrob Agents Chemother. 2017;61(5):e00111-17. Published 2017 Apr 24. doi:10.1128/AAC.00111-17


Pharmacokinetics of Clindamycin in Obese and Nonobese Children

Clindamycin concentrations collected from the three trials were quantified using a validated liquid chromatography-tandem spectrometry assay.   The lower limit of quantification was 50 ng/mL.

Smith MJ, Gonzalez D, Goldman JL, et al. Antimicrob Agents Chemother. 2017;61(4):e02014-16. Published 2017 Mar 24. doi:10.1128/AAC.02014-16


Clustering of PCOS-like traits in naturally hyperandrogenic female rhesus monkeys

Steroid hormones were separated and quantified using high-performance liquid chromatography followed by tandem mass spectrometry (HPLC-MS/MS).   The lower detection limits were: androstenedione (A4), 0.1 ng/mL; cortisol and dehydroepiandrosterone (DHEA), 0.5 ng/mL; corticosterone, 11-deoxycortisol and deoxycorticosterone (DOC), 0.05 ng/mL; estradiol (E2) and estrone, 5 pg/mL; 17-hydroxyprogesterone (17-OHP) and progesterone, 0.2 ng/mL and Testosterone (T), 0.02 ng/mL.

Abbott DH, Rayome BH, Dumesic DA, et al. Hum Reprod. 2017;32(4):923-936. doi:10.1093/humrep/dex036


Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants

Clindamycin concentrations were quantified using a validated liquid chromatography-tandem mass spectrometry assay.   The lower limit of quantification was 50 ng/mL.

Gonzalez D, Delmore P, Bloom BT, et al. Antimicrob Agents Chemother. 2016;60(5):2888-2894. Published 2016 Apr 22. doi:10.1128/AAC.03086-15


High-Throughput Screening of Chemical Effects on Steroidogenesis Using H295R Human Adrenocortical Carcinoma Cells

Steroid hormones were quantified using high-performance liquid chromatography followed by tandem mass spectrometry (HPLC-MS/MS).   The lower detection limits varied depending upon analyte.   Steroid hormones were extracted from media samples using methyl tert-butyl ether (MTBE).   An extra derivatization with dansyl chloride was included for estrogen (estrone and estradiol) detection only.

Karmaus AL, Toole CM, Filer DL, Lewis KC, Martin MT. Toxicol Sci. 2016;150(2):323-332. doi:10.1093/toxsci/kfw002


Exposure of Female Rats to an Environmentally Relevant Mixture of Brominated Flame Retardants Targets the Ovary, Affecting Folliculogenesis and Steroidogenesis

Steroid hormones, including pregnenolone, progesterone, 17-OH pregnenolone, 17-OH progesterone, dihydroepiandrosterone, androstenedione, testosterone, and dihydrotestosterone (DHT), were measured in 100-μl serum samples by high-performance liquid chromatography system interfaced to an Agilent Triple Quad LC/MS.

Lefèvre PL, Berger RG, Ernest SR, et al. Biol Reprod. 2016;94(1):9. doi:10.1095/biolreprod.115.134452


VT-1161 Protects Immunosuppressed Mice from Rhizopus arrhizus var. arrhizus Infection

VT-1161 plasma levels were measured by liquid chromatography-tandem mass spectrometry (LC/MS-MS).

Gebremariam T, Wiederhold NP, Fothergill AW, et al. Antimicrob Agents Chemother. 2015;59(12):7815-7817. doi:10.1128/AAC.01437-15


Evaluation of VT-1161 for Treatment of Coccidioidomycosis in Murine Infection Models

VT-1161 was extracted from plasma samples with methyl tert-butyl ether.   Samples were analyzed using high-performance liquid chromatography with tandem mass spectrometry using electrospray ionization.

Shubitz LF, Trinh HT, Galgiani JN, et al. Antimicrob Agents Chemother. 2015;59(12):7249-7254. doi:10.1128/AAC.00593-15


Efficacy of the Clinical Agent VT-1161 against Fluconazole-Sensitive and -Resistant Candida albicans in a Murine Model of Vaginal Candidiasis

VT-1161 was extracted from plasma samples with methyl tert-butyl ether.   Samples (plasma and vaginal tissues) were analyzed using high-performance liquid chromatography with tandem mass spectrometry using electrospray ionization.

Garvey EP, Hoekstra WJ, Schotzinger RJ, Sobel JD, Lilly EA, Fidel PL Jr. Antimicrob Agents Chemother. 2015;59(9):5567-5573. doi:10.1128/AAC.00185-15


Safety and Pharmacokinetics of Lisinopril in Pediatric Kidney Transplant Recipients

The concentration of lisinopril in plasma and urine was measured using high-pressure liquid chromatography–tandem mass spectrometry (HPLC-MS/MS).   For plasma, the lower limit of quantification was 0.5 ng/mL, and for urine the lower limit of quantification was 50 ng/mL.

Trachtman H, Frymoyer A, Lewandowski A, et al. Clin Pharmacol Ther. 2015;98(1):25-33. doi:10.1002/cpt.127


Simultaneous Determination of Trimethoprim and Sulfamethoxazole in Dried Plasma and Urine Spots

A precise, accurate and reproducible HPLC–MS/MS method was validated and applied to simultaneously quantify trimethoprim-sulfamethoxazole in dried plasma spots and dried urine spots samples collected in an opportunistic pediatric study.   The LLOQ for trimethoprim was 100 ng/mL in dried plasma spots and 500 ng/mL in dried urine spots samples; for sulfamethoxazole, the LLOQ was 1000 ng/mL for both matrices.

Gonzalez D, Melloni C, Poindexter BB, et al. Bioanalysis. 2015;7(9):1137-1149. doi:10.4155/bio.15.38


VT-1161 Dosed Once Daily or Once Weekly Exhibits Potent Efficacy in Treatment of Dermatophytosis in a Guinea Pig Model

Collected samples (plasma, skin and hair) were analyzed using liquid chromatography-tandem mass spectrometry (LC/MS-MS) with electrospray ionization following extraction with methyl tert-butyl ether (MTBE).

Garvey EP, Hoekstra WJ, Moore WR, Schotzinger RJ, Long L, Ghannoum MA. Antimicrob Agents Chemother. 2015;59(4):1992-1997. doi:10.1128/AAC.04902-14


The Clinical Candidate VT-1161 Is a Highly Potent Inhibitor of Candida albicans CYP51 but Fails To Bind the Human Enzyme

In vitro ADME CYP2C9, CYP2C19, and CYP3A4 assays.

Warrilow AG, Hull CM, Parker JE, et al. Antimicrob Agents Chemother. 2014;58(12):7121-7127. doi:10.1128/AAC.03707-14


Use of Opportunistic Clinical Data and a Population Pharmacokinetic Model to Support Dosing of Clindamycin for Premature Infants to Adolescents

Clindamycin in plasma was quantified using a validated liquid chromatography-tandem spectrometry (LC-MS/MS) assay.   The validation range for the assay was 50–50,000 ng/mL.

Gonzalez D, Melloni C, Yogev R, et al. Clin Pharmacol Ther. 2014;96(4):429-437. doi:10.1038/clpt.2014.134


Characterization of the Population Pharmacokinetics of Ampicillin in Neonates Using an Opportunistic Study Design

Ampicillin concentrations were determined using a validated bioanalytical high-pressure liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay.   The validated range of this method for ampicillin based on 10 μLs of human plasma was 0.05 to 50 μg/mL.

Tremoulet A, Le J, Poindexter B, et al. Antimicrob Agents Chemother. 2014;58(6):3013-3020. doi:10.1128/AAC.02374-13


Synthesis, metabolic stability and antiviral evaluation of various alkoxyalkyl esters of cidofovir and 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine

Test articles were incubated in Liver S9 fractions at 37 °C.   Samples were pulled from the incubation mixture at specified time points (0 to 90 minutes) and added to a solution of 1% ammonium hydroxide in N-propyl alcohol.   The amount of test article in each sample was quantified by HPLC/MS/MS.

Ruiz J, Beadle JR, Buller RM, et al. Bioorg Med Chem. 2011;19(9):2950-2958. doi:10.1016/j.bmc.2011.03.034


Development of hexadecyloxypropyl tenofovir (CMX157) for treatment of infection caused by wild-type and nucleoside/nucleotide-resistant HIV

Analyses of the PBMC samples to determine concentrations of the nucleotide analog TFV and anabolites TFV-MP and TFV-PP were performed utilizing high-performance liquid chromatography (HPLC) with tandem mass spectrometric detection (MS/MS).   TFV, TFV-MP, and TFV-PP were separated by gradient, reverse-phase, ion-pairing chromatography and detected by positive-ion electrospray.

Lanier ER, Ptak RG, Lampert BM, et al. Antimicrob Agents Chemother. 2010;54(7):2901-2909. doi:10.1128/AAC.00068-10