Nitrosamine Contamination in Pharmaceuticals: Threat,Impact, and Control |
| |
Affiliation: | Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phayathai Rd., Bangkok 10330, Thailand |
| |
Abstract: | Nitrosamine-contaminated medicinal products have raised safety concerns towards the use of various drugs, not only valsartan and all tetrazole-containing angiotensin II receptor blockers, but also ranitidine, metformin, and other medicines, many of which have been recalled and prone to shortage. At any stages, from drug substance synthesis throughout each product's lifetime, these impurities may evolve if an amine reacts with a nitrosating agent coexisting under appropriate conditions. Consequently, drug regulatory authorities worldwide have established stringent guidelines on nitrosamine contamination for all drug products in the market. This review encompasses various critical elements contributing to successful control measures against current and upcoming nitrosamine issues, ranging from accumulated knowledge of their toxicity concerns and potential root causes, precise risk evaluation, as well as suitable analytical techniques with sufficient sensitivity for impurity determination. With all these tools equipped, the impact of nitrosamine contamination in pharmaceuticals should be mitigated. An evaluation aid to tackle challenges in risk identification, as well as suitable industry-friendly analytical techniques to determine nitrosamines and other mutagenic impurities, are among unmet needs that will significantly simplify the risk assessment process. |
| |
Keywords: | Nitrosamine NDMA Angiotensin II receptor blockers A" },{" #name" :" keyword" ," $" :{" id" :" key0002" }," $$" :[{" #name" :" text" ," _" :" adenine Asp" },{" #name" :" keyword" ," $" :{" id" :" key0004" }," $$" :[{" #name" :" text" ," _" :" aspartic acid APCI" },{" #name" :" keyword" ," $" :{" id" :" key0006" }," $$" :[{" #name" :" text" ," _" :" atmospheric pressure chemical ionization API" },{" #name" :" keyword" ," $" :{" id" :" key0008" }," $$" :[{" #name" :" text" ," _" :" active pharmaceutical ingredient ARBs" },{" #name" :" keyword" ," $" :{" id" :" key0010" }," $$" :[{" #name" :" text" ," _" :" angiotensin II receptor blockers BP" },{" #name" :" keyword" ," $" :{" id" :" key0012" }," $$" :[{" #name" :" text" ," _" :" British Pharmacopoeia C" },{" #name" :" keyword" ," $" :{" id" :" key0014" }," $$" :[{" #name" :" text" ," _" :" cytosine CPNP" },{" #name" :" keyword" ," $" :{" id" :" key0016" }," $$" :[{" #name" :" text" ," _" :" 1-cyclopentyl-4-nitrosopiperazine DIPEA" },{" #name" :" keyword" ," $" :{" id" :" key0018" }," $$" :[{" #name" :" text" ," _" :" N,N-diisopropylethylamine DMF" },{" #name" :" keyword" ," $" :{" id" :" key0020" }," $$" :[{" #name" :" text" ," _" :" N,N-dimethylformamide DNAs" },{" #name" :" keyword" ," $" :{" id" :" key0022" }," $$" :[{" #name" :" text" ," _" :" deoxyribonucleic acids EDQM" },{" #name" :" keyword" ," $" :{" id" :" key0024" }," $$" :[{" #name" :" text" ," _" :" European Directorate for the Quality of Medicines & HealthCare EMA" },{" #name" :" keyword" ," $" :{" id" :" key0026" }," $$" :[{" #name" :" text" ," _" :" European Medicine Agency ESI" },{" #name" :" keyword" ," $" :{" id" :" key0028" }," $$" :[{" #name" :" text" ," _" :" electrospray ionization G" },{" #name" :" keyword" ," $" :{" id" :" key0030" }," $$" :[{" #name" :" text" ," _" :" guanine GC–MS/MS" },{" #name" :" keyword" ," $" :{" id" :" key0032" }," $$" :[{" #name" :" text" ," _" :" gas chromatographs-tandem mass spectrometers HRMS" },{" #name" :" keyword" ," $" :{" id" :" key0034" }," $$" :[{" #name" :" text" ," _" :" high-resolution mass spectrometer IARC" },{" #name" :" keyword" ," $" :{" id" :" key0036" }," $$" :[{" #name" :" text" ," _" :" International Agency for Research on Cancer ICH" },{" #name" :" keyword" ," $" :{" id" :" key0038" }," $$" :[{" #name" :" text" ," _" :" International Council for harmonization of Technical Requirements for Pharmaceuticals for Human Use LC-MS/MS" },{" #name" :" keyword" ," $" :{" id" :" key0040" }," $$" :[{" #name" :" text" ," _" :" liquid chromatographs-tandem mass spectrometers LOQ" },{" #name" :" keyword" ," $" :{" id" :" key0042" }," $$" :[{" #name" :" text" ," _" :" limit of quantification MNP" },{" #name" :" keyword" ," $" :{" id" :" key0044" }," $$" :[{" #name" :" text" ," _" :" 1-methyl-4-nitrosopiperazine NDEA" },{" #name" :" keyword" ," $" :{" id" :" key0046" }," $$" :[{" #name" :" text" ," _" :" N-nitrosodiethylamine NDIPA" },{" #name" :" keyword" ," $" :{" id" :" key0048" }," $$" :[{" #name" :" text" ," _" :" N-nitrosodiisopropylamine NDMA" },{" #name" :" keyword" ," $" :{" id" :" key0050" }," $$" :[{" #name" :" text" ," _" :" N-nitrosodimethylamine NEIPA" },{" #name" :" keyword" ," $" :{" id" :" key0052" }," $$" :[{" #name" :" text" ," _" :" N-nitrosoethylisopropylamine NMBA" },{" #name" :" keyword" ," $" :{" id" :" key0054" }," $$" :[{" #name" :" text" ," _" :" N-nitroso-N-methyl-4-aminobutyric acid NMP" },{" #name" :" keyword" ," $" :{" id" :" key0056" }," $$" :[{" #name" :" text" ," _" :" N-methyl pyrrolidinone Ph. Eur." },{" #name" :" keyword" ," $" :{" id" :" key0058" }," $$" :[{" #name" :" text" ," _" :" European Pharmacopoeia Ph. Int." },{" #name" :" keyword" ," $" :{" id" :" key0060" }," $$" :[{" #name" :" text" ," _" :" International Pharmacopoeia QQQ" },{" #name" :" keyword" ," $" :{" id" :" key0062" }," $$" :[{" #name" :" text" ," _" :" triple quadrupole QTRAP" },{" #name" :" keyword" ," $" :{" id" :" key0064" }," $$" :[{" #name" :" text" ," _" :" quadrupole-ion trap SPE" },{" #name" :" keyword" ," $" :{" id" :" key0066" }," $$" :[{" #name" :" text" ," _" :" solid phase extraction SPME" },{" #name" :" keyword" ," $" :{" id" :" key0068" }," $$" :[{" #name" :" text" ," _" :" solid phase microextraction T" },{" #name" :" keyword" ," $" :{" id" :" key0070" }," $$" :[{" #name" :" text" ," _" :" thymine Tyr" },{" #name" :" keyword" ," $" :{" id" :" key0072" }," $$" :[{" #name" :" text" ," _" :" tyrosine U.S. FDA" },{" #name" :" keyword" ," $" :{" id" :" key0074" }," $$" :[{" #name" :" text" ," _" :" U.S. Food and Drug Administration USP" },{" #name" :" keyword" ," $" :{" id" :" key0076" }," $$" :[{" #name" :" text" ," _" :" United States Pharmacopeia WHO" },{" #name" :" keyword" ," $" :{" id" :" key0078" }," $$" :[{" #name" :" text" ," _" :" World Health Organization |
本文献已被 ScienceDirect 等数据库收录! |
|