A solvent-free headspace GC/MS method for sensitive screening of: N -nitrosodimethylamine in drug products

Do Hee Lee; Su Hyeon Hwang; Seoungchul Park; Jeongmi Lee; Han Bin Oh; Sang Beom Han; Kwang Hyun Liu; Yong Moon Lee; Hee Soo Pyo; Jongki Hong

doi:10.1039/d1ay01036k

A solvent-free headspace GC/MS method for sensitive screening of: N -nitrosodimethylamine in drug products

Do Hee Lee, Su Hyeon Hwang, Seoungchul Park, Jeongmi Lee, Han Bin Oh, Sang Beom Han, Kwang Hyun Liu, Yong Moon Lee, Hee Soo Pyo, Jongki Hong

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

A solvent-free headspace gas chromatography-mass spectrometry (SF-HS-GC/MS) method was developed and validated for screening N-nitrosodimethylamine (NDMA) in various active pharmaceutical ingredients (APIs) and drug products. Experimental parameters such as incubation temperature, incubation time, and sample volume in solvent-free headspace conditions were optimized. The developed SF-HS-GC/MS method was validated in terms of linearity, limit of quantification (LOQ), precision, and accuracy. The results indicated excellent linearity from 5 to 500 ng g-1 with correlation coefficients higher than 0.9999. The LOQ of this method was 5 ng g-1 and matrix effects ranged from 0.97 to 1.11. The accuracy ranged from 92.77 to 106.54% and the precision RSDs were below 5.94%. No significant matrix effect was observed for any of the drug products. Also, artefactual NDMA formation in ranitidine, nizatidine, and metformin was investigated under HS conditions. Adjusted (mild) SF-HS conditions were suggested for precise quantification of NDMA in positive drug products by GC/MS. The present SF-HS-GC/MS method is a promising tool for the screening and determination of toxic NDMA in APIs and drug products.

Original language	English
Pages (from-to)	3402-3409
Number of pages	8
Journal	Analytical Methods
Volume	13
Issue number	30
DOIs	https://doi.org/10.1039/d1ay01036k
State	Published - 14 Aug 2021

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@article{d25c1a01c9b149ba970538657134b13a,

title = "A solvent-free headspace GC/MS method for sensitive screening of: N -nitrosodimethylamine in drug products",

abstract = "A solvent-free headspace gas chromatography-mass spectrometry (SF-HS-GC/MS) method was developed and validated for screening N-nitrosodimethylamine (NDMA) in various active pharmaceutical ingredients (APIs) and drug products. Experimental parameters such as incubation temperature, incubation time, and sample volume in solvent-free headspace conditions were optimized. The developed SF-HS-GC/MS method was validated in terms of linearity, limit of quantification (LOQ), precision, and accuracy. The results indicated excellent linearity from 5 to 500 ng g-1 with correlation coefficients higher than 0.9999. The LOQ of this method was 5 ng g-1 and matrix effects ranged from 0.97 to 1.11. The accuracy ranged from 92.77 to 106.54\% and the precision RSDs were below 5.94\%. No significant matrix effect was observed for any of the drug products. Also, artefactual NDMA formation in ranitidine, nizatidine, and metformin was investigated under HS conditions. Adjusted (mild) SF-HS conditions were suggested for precise quantification of NDMA in positive drug products by GC/MS. The present SF-HS-GC/MS method is a promising tool for the screening and determination of toxic NDMA in APIs and drug products.",

author = "Lee, \{Do Hee\} and Hwang, \{Su Hyeon\} and Seoungchul Park and Jeongmi Lee and Oh, \{Han Bin\} and Han, \{Sang Beom\} and Liu, \{Kwang Hyun\} and Lee, \{Yong Moon\} and Pyo, \{Hee Soo\} and Jongki Hong",

note = "Publisher Copyright: {\textcopyright} The Royal Society of Chemistry.",

year = "2021",

month = aug,

day = "14",

doi = "10.1039/d1ay01036k",

language = "English",

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journal = "Analytical Methods",

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T1 - A solvent-free headspace GC/MS method for sensitive screening of

T2 - N -nitrosodimethylamine in drug products

AU - Lee, Do Hee

AU - Hwang, Su Hyeon

AU - Park, Seoungchul

AU - Lee, Jeongmi

AU - Oh, Han Bin

AU - Han, Sang Beom

AU - Liu, Kwang Hyun

AU - Lee, Yong Moon

AU - Pyo, Hee Soo

AU - Hong, Jongki

PY - 2021/8/14

Y1 - 2021/8/14

N2 - A solvent-free headspace gas chromatography-mass spectrometry (SF-HS-GC/MS) method was developed and validated for screening N-nitrosodimethylamine (NDMA) in various active pharmaceutical ingredients (APIs) and drug products. Experimental parameters such as incubation temperature, incubation time, and sample volume in solvent-free headspace conditions were optimized. The developed SF-HS-GC/MS method was validated in terms of linearity, limit of quantification (LOQ), precision, and accuracy. The results indicated excellent linearity from 5 to 500 ng g-1 with correlation coefficients higher than 0.9999. The LOQ of this method was 5 ng g-1 and matrix effects ranged from 0.97 to 1.11. The accuracy ranged from 92.77 to 106.54% and the precision RSDs were below 5.94%. No significant matrix effect was observed for any of the drug products. Also, artefactual NDMA formation in ranitidine, nizatidine, and metformin was investigated under HS conditions. Adjusted (mild) SF-HS conditions were suggested for precise quantification of NDMA in positive drug products by GC/MS. The present SF-HS-GC/MS method is a promising tool for the screening and determination of toxic NDMA in APIs and drug products.

AB - A solvent-free headspace gas chromatography-mass spectrometry (SF-HS-GC/MS) method was developed and validated for screening N-nitrosodimethylamine (NDMA) in various active pharmaceutical ingredients (APIs) and drug products. Experimental parameters such as incubation temperature, incubation time, and sample volume in solvent-free headspace conditions were optimized. The developed SF-HS-GC/MS method was validated in terms of linearity, limit of quantification (LOQ), precision, and accuracy. The results indicated excellent linearity from 5 to 500 ng g-1 with correlation coefficients higher than 0.9999. The LOQ of this method was 5 ng g-1 and matrix effects ranged from 0.97 to 1.11. The accuracy ranged from 92.77 to 106.54% and the precision RSDs were below 5.94%. No significant matrix effect was observed for any of the drug products. Also, artefactual NDMA formation in ranitidine, nizatidine, and metformin was investigated under HS conditions. Adjusted (mild) SF-HS conditions were suggested for precise quantification of NDMA in positive drug products by GC/MS. The present SF-HS-GC/MS method is a promising tool for the screening and determination of toxic NDMA in APIs and drug products.

UR - https://www.scopus.com/pages/publications/85112182055

U2 - 10.1039/d1ay01036k

DO - 10.1039/d1ay01036k

M3 - Article

C2 - 34250988

AN - SCOPUS:85112182055

SN - 1759-9660

VL - 13

SP - 3402

EP - 3409

JO - Analytical Methods

JF - Analytical Methods

IS - 30

ER -

A solvent-free headspace GC/MS method for sensitive screening of: N -nitrosodimethylamine in drug products

Abstract

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