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Direct Drug Analysis in Polymeric Implants Using Desorption Electrospray Ionization – Mass Spectrometry Imaging (DESI-MSI)

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Abstract

Purpose

Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) coupled with gas-phase ion mobility spectrometry was used to characterize the drug distribution in polymeric implants before and after exposure to accelerated in vitro release (IVR) media. DESI-MSI provides definitive chemical identification and localization of formulation components, including 2D chemical mapping of individual components with essentially no sample preparation.

Methods

Polymeric implants containing 40% (w/w) entecavir and poly(D,L-lactide) (PLA) were prepared and then exposed to either acidified PBS (pH 2.5) or MeOH:H2O (50:50, v/v) medias during a 7-day IVR test using continuous flow-through (CFT) cell dissolution. The amount of drug released from the polymer matrix during the 7-day IVR test was monitored by online-ultraviolet spectroscopy (UV) and HPLC-UV. After that period, intact implants and radial sections of implants were analyzed by DESI-MSI with ion mobility spectrometry. The active ingredient along with impurities and contaminants were used to generate chemical maps before and after exposure to the release medias.

Results

Bi-phasic release profiles were observed for implants during IVR release using both medias. During the second phase of release, implants exposed to PBS, pH 2.5, released the entecavir faster than the implants exposed to MeOH:H2O (50:50, v/v). Radial images of the polymer interior show that entecavir is localized along the central core of the implant after exposure to MeOH:H2O (50:50, v/v) and that the drug is more uniformly distributed throughout the implant after exposure to acidified PBS (pH 2.5).

Conclusions

DESI-MSI coupled with ion mobility analysis produced chemical images of the drug distribution on the exterior and interior of cylindrical polymeric implants before and after exposure to various release medias. These results demonstrated the utility of this technique for rapid characterization of drug and impurity/degradant distribution within polymeric implants with direct implications for formulation development as well as analytical method development activities for various solid parenteral and oral dosage forms. These results are especially meaningful since samples were analyzed with essentially no preparative procedures.

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Abbreviations

API:

Active Pharmaceutical Ingredient

CFT:

Continuous flow-through

DESI:

Desorption electrospray ionization

HDI:

High definition imaging

HDMS:

High-definition mass spectrometry

HPLC:

High-performance liquid chromatography

IM:

Intramuscular

IMS:

Ion mobility spectrometry

LAP:

Long-acting parenteral

MSI:

Mass spectrometry imaging

PBS:

Phosphate-buffered saline

PLA:

Poly(D,L-lactide)

SC:

Subcutaneous

TIC:

Total ion chromatogram

USP:

United States Pharmacopeia

UV:

Ultraviolet

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors would like to thank Ray Seto for his assistance with producing radial sections of the implants. Additionally, a special thanks to Stephanie Barrett, Justin Pennington, Paul Walsh, and W. Peter Wuelfing for their helpful insights and discussions. Financial support for this work was provided by Merck & Co., Inc., Kenilworth, NJ, USA and Waters Corporation, Beverly, MA, USA.

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Author notes

  1. Alena Bensussan

    Present address: Department of Chemistry, The University of Texas at Austin, Austin, Texas, 78712, USA

Authors and Affiliations

  1. Merck Research Laboratories, Merck & Co., Inc., Rahway, New Jersey, 07065, USA

    Elizabeth E. Pierson, William P. Forrest, Vivek Shah, Seth Forster, Alena Bensussan & Roy Helmy

  2. Waters Corporation, Beverly, Massachusetts, 01915, USA

    Anthony J. Midey, Hernando J. Olivos, Bindesh Shrestha & Ryan Teller

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  1. Elizabeth E. Pierson
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Correspondence to Elizabeth E. Pierson.

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Pierson, E.E., Midey, A.J., Forrest, W.P. et al. Direct Drug Analysis in Polymeric Implants Using Desorption Electrospray Ionization – Mass Spectrometry Imaging (DESI-MSI). Pharm Res 37, 107 (2020). https://doi.org/10.1007/s11095-020-02823-x

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