HILIC-MS determination of dimethylamine in the active pharmaceutical ingredients and in the dosage forms of metformin

Douša, Michal; Jireš, Jakub

doi:10.1016/j.jpba.2020.113573

Cited by 10 publications

(4 citation statements)

References 15 publications

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“…The LOD of DMA is about 1000 times lower than headspace gas chromatography method (930 μg/L) [ 17 ]. The reported LOD of DMA is 5.4 μg/L by HPLC with diode array detection after derivatization with halonitrobenzenes, and 0.75 μg/L by hydrophilic interaction chromatography coupled with mass spectrometry detection (HILIC-MS) [ 11 , 18 ]. The LOD of DMA using our method is close to HILIC-MS method without the need of a high-cost mass spectrometer.…”

Section: Resultsmentioning

confidence: 99%

Determination of dimethylamine and nitrite in pharmaceuticals by ion chromatography to assess the likelihood of nitrosamine formation

Christison

Rohrer

2021

Heliyon

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Since July 2018 several drugs have been recalled due to contamination with N -nitrosodimethylamine (NDMA), a probable human carcinogen. Dimethylamine (DMA) and nitrite are precursors in the formation of NDMA. In this study, ion chromatography (IC) methods were developed for the determination of these two precursors in drug substances and drug products. Two methods were developed to determine DMA in two drug products using a cation exchange separation coupled to suppressed conductivity detection. The limit of detection of DMA is < 1 μg/g of active pharmaceutical ingredient (API) for both methods. Nitrite was determined using an anion exchange separation coupled with UV absorbance detection. The limit of detection of nitrite was 0.918 μg/g API. The developed methods were successfully applied to DMA and nitrite determinations in five drug products including metformin, losartan, ranitidine, Nytol, and Benadyrl, and two drug substances (APIs), losartan potassium and metformin hydrochloride. Some samples contained nitrite and DMA at detectable levels. Dimethylamine and nitrite recovery from pharmaceutical samples ranged from 96.0-104 %. The developed methods should be useful for the rapid screening and quantification of nitrite and DMA in pharmaceuticals and in-process samples to assess the likelihood of NDMA formation. The methods for DMA should be applicable to other amines to assess the likelihood of the formation of other nitrosamines in pharmaceutical products.

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Section: Resultsmentioning

confidence: 99%

Determination of dimethylamine and nitrite in pharmaceuticals by ion chromatography to assess the likelihood of nitrosamine formation

Christison

Rohrer

2021

Heliyon

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“…Thus, N , N ‐dimethylaniline belongs to the class of pH‐dependent analytes (Liigand et al, 2021). Similarly, the quantitation of dimethylamine in metformin drug products was carried out using a mobile phase containing ammonium formate pH 4.8 in ESI + (Douša & Jireš, 2020).…”

Section: Ms‐based Methods In the Analysis Of Small‐molecule Chemical ...mentioning

confidence: 99%

What is the role of current mass spectrometry in pharmaceutical analysis?

Khalikova

Jireš

Horáček

et al. 2023

Mass Spectrometry Reviews

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The role of mass spectrometry (MS) has become more important in most application domains in recent years. Pharmaceutical analysis is specific due to its stringent regulation procedures, the need for good laboratory/manufacturing practices, and a large number of routine quality control analyses to be carried out. The role of MS is, therefore, very different throughout the whole drug development cycle. While it dominates within the drug discovery and development phase, in routine quality control, the role of MS is minor and indispensable only for selected applications. Moreover, its role is very different in the case of analysis of small molecule pharmaceuticals and biopharmaceuticals. Our review explains the role of current MS in the analysis of both small‐molecule chemical drugs and biopharmaceuticals. Important features of MS‐based technologies being implemented, method requirements, and related challenges are discussed. The differences in analytical procedures for small molecule pharmaceuticals and biopharmaceuticals are pointed out. While a single method or a small set of methods is usually sufficient for quality control in the case of small molecule pharmaceuticals and MS is often not indispensable, a large panel of methods including extensive use of MS must be used for quality control of biopharmaceuticals. Finally, expected development and future trends are outlined.

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“…1,7-Diaminoheptane (Dah) (1 μM × 0.1 mL) was added to 1 mL of extract as an internal standard. Diamines and aminoamides in the extractants were analyzed by HILIC-ESI-MS/MS (LCMS-8040, Shimadzu, Kyoto, Japan). − Chromatographic separation was performed with a HILIC column (HILICpak VC-50 2D, Shodex, Tokyo, Japan) and an eluent of 0.2 M formic acid at a flow rate of 0.20 mL/min in isocratic mode. The eluted target compounds were detected with the mass spectrometer by selected reaction monitoring (SRM) (see Table S1 in the Supporting Information for SRM settings).…”

Section: Methodsmentioning

confidence: 99%

Biogenic Diamines and Their Amide Derivatives Are Present in the Forest Atmosphere and May Play a Role in Particle Formation

Saeki

Ikari

Yokoi

et al. 2022

ACS Earth Space Chem.

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Diamines, such as 1,3-diaminopropane (Dap), 1,4-diaminobutane (putrescine, or Put), and 1,5-diaminopentane (cadaverine), are essential organic bases for plants. Such “biogenic diamines” are abundantly present in oak tree flowers and are emitted into the atmosphere. We sampled atmospheric diamines in a typical broadleaf tree forest and chestnut grove during blossom season and carried out a chromatography-mass spectrometry analysis. Amide derivatives of Dap and Put, 3-aminopropanamide and 4-aminobutanamide, respectively, were found in higher atmospheric concentrations than their source diamine. Because their concentrations in oak tree flowers were very low, we deduced that these aminoamides were produced after Dap and Put, respectively, were released into the atmosphere. Time series of biogenic diamine and aminoamide concentrations showed evidence of diurnal variations. Concentrations were lower during daytime in sunny conditions, suggesting relatively fast photochemical decomposition. Biogenic diamines and aminoamides bond more easily than monoamines with water vapor and sulfuric acid in the atmosphere. Biogenic diamines and aminoamides may play a role in the formation of new particles and biogenic secondary organic aerosols in the forest atmosphere during spring and early summer.

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HILIC-MS determination of dimethylamine in the active pharmaceutical ingredients and in the dosage forms of metformin

Cited by 10 publications

References 15 publications

Determination of dimethylamine and nitrite in pharmaceuticals by ion chromatography to assess the likelihood of nitrosamine formation

Determination of dimethylamine and nitrite in pharmaceuticals by ion chromatography to assess the likelihood of nitrosamine formation

What is the role of current mass spectrometry in pharmaceutical analysis?

Biogenic Diamines and Their Amide Derivatives Are Present in the Forest Atmosphere and May Play a Role in Particle Formation

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