Detection of gabapentin-lactose Maillard reaction product (Schiff's Base): Application to solid dosage form preformulation. Part 1

Monajjemzadeh, Farnaz, Hassanzadeh, Davoud, Valizadeh, Hadi, Siahi-Shadbad, Mohammad R., Mojarrad, Javid Shahbazi, Robertson, Thomas A. and Roberts, Michael S. (2011) Detection of gabapentin-lactose Maillard reaction product (Schiff's Base): Application to solid dosage form preformulation. Part 1. pharmind: Die Pharmazeutische Industrie, 73 1: 174-177.

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Author Monajjemzadeh, Farnaz
Hassanzadeh, Davoud
Valizadeh, Hadi
Siahi-Shadbad, Mohammad R.
Mojarrad, Javid Shahbazi
Robertson, Thomas A.
Roberts, Michael S.
Title Detection of gabapentin-lactose Maillard reaction product (Schiff's Base): Application to solid dosage form preformulation. Part 1
Journal name pharmind: Die Pharmazeutische Industrie   Check publisher's open access policy
Translated journal name pharmind: The Pharmaceutical Industry
Language of Journal Name ger
ISSN 0031-711X
1616-7074
Publication date 2011-01-01
Sub-type Article (original research)
Volume 73
Issue 1
Start page 174
End page 177
Total pages 4
Place of publication Aulendorf, Germany
Publisher Editio Cantor
Language eng
ger
Formatted abstract
In the following study several techniques are utilized such as Differential Scanning Calorimetery (DSC), Infra-Red (IR) spectroscopy, High Performance Liquid Chromatography (HPLC) and Liquid Chromatography–Mass Spectrometry/Mass Spectrometry (LC-MS/MS) to characterize gabapentin (GBP) and lactose incompatibility in solid state binary mixtures and also in different capsule brands. Solid and aqueous mixtures of the drug and excipient were heated in order to prepare the adduct mixture. Based on the DSC results incompatibility was demonstrated and the imine formation was subsequently evaluated using FTIR spectra. HPLC analysis revealed two extra peaks (compound 1G and 2G) that were fractionated and then injected into LC-MS/MS system. Mass spectra of compound 2G was successfully correlated to GBP-lactose Maillard reaction product. The MRM (Multiple Reaction Monitoring) achieved using a new internal standard and was capable of detecting 4 separate peaks. The LC-MS/MS method was validated and then used for quantifying the amount of remaining drug in the test samples. The presence of lactose in commercial capsules was checked using a TLC method. Overall, the incompatibility of GBP with lactose was successfully evaluated using a combination of thermal methods, FTIR, HPLC and LC-MS/MS.

In der folgenden Studie werden verschiedene Verfahren angewandt, um die Inkompatibilität von Gabapentin und Lactose in Trockenmischungen und verschiedenen Kapselpräparaten zu charakterisieren: dynamische Differentialkalorimetrie (DSC), Infrarot-Spektroskopie (IR), Hochleistungsflüssigkeitschromatographie (HPLC) und Flüssigkeitschromatographie–Massenspektroskopie/Massenspektroskopie (LC-MS/MS). Trockene und wässrige Mischungen von Wirk- und Hilfsstoff wurden zur Vorbereitung erwärmt. Auf der Grundlage von DSC wurde die Inkompatibilität gezeigt und nachfolgend die Imin-Bildung mittels FTIR-Spektren evaluiert. Die HPLC-Analyse ergab zwei gesonderte Peaks (Substanzen 1G und 2G), die fraktioniert und dann in das LC-MS/MS-System injiziert wurden. Die Massenspektren von Substanz 2G konnten mit dem Maillard-Reaktionsprodukt von Gabapentin und Lactose korreliert werden. MRM (Multiple Reaction Monitoring) ergab die Verwendung eines neuen internen Standards und konnte 4 getrennte Peaks detektieren. Die LC-MS/MS-Methode wurde validiert und zur Bestimmung des Wirkstoff-Restgehalts in den Proben verwendet. Schließlich wurde die Anwesenheit von Lactose in handelsüblichen Kapseln mittels TLC geprüft. Insgesamt wurde die Inkompatibilität von Gabapentin und Lactose bestätigt – mit einer Kombination von thermischen Methoden, FTIR, HPLC und LC-LC/MS.
Keyword Differential scanning calorimetry
Fourier-transform infrared spectroscopy
Gabapentin, lactose incompatibility
High Performance Liquid Chromatograpyh
Lactose, gabapentin incompatibility
Liquid chromatography-mass spectrometry/mass spectrometry
Solid state
High Performance Liquid Chromatography
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article in English, abstract only in German.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
 
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Created: Sun, 13 Mar 2011, 10:06:04 EST