title: Critical practical aspects in the application of liquid chromatography-mass spectrometric studies for the characterization of impurities and degradation products.
abstract: Liquid chromatography-mass spectrometry (LC-MS) is considered today as a mainstay tool for the structure characterization of minor components like impurities (IMPs) and degradation products (DPs) in drug substances and products. A multi-step systematic strategy for the purpose involves high resolution mass and multi-stage mass studies on both the drug and IMPs/DPs, followed by comparison of their fragmentation profiles. Its successful application requires consideration of many practical aspects at each step. The same are critically discussed in this review.
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar 160062, Punjab, India.
authors.forename: Mallikarjun
authors.initials: M
authors.lastname: Narayanam
authors.forename: Tarun
authors.initials: T
authors.lastname: Handa
authors.forename: Parul
authors.initials: P
authors.lastname: Sharma
authors.forename: Shalu
authors.initials: S
authors.lastname: Jhajra
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Muthe
authors.forename: Pavan Kumar
authors.initials: PK
authors.lastname: Dappili
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Shah
authors.forename: Saranjit
authors.initials: S
authors.lastname: Singh
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D004340:Drug Contamination; D013058:Mass Spectrometry / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry / Q000592:standards
chemical_list: D004364:Pharmaceutical Preparations
keywords: (4-hydrazino-4-oxobutyl) tris(2,4,6-trimethoxyphenyl) phosphonium bromide; 1,2-dimethylimidazole-4-sulfonyl; 1-(2,4-dinitro-5-fluorophenyl)-4-methylpiperazine; 1-(carboxymethyl) pyridium chloride hydrazide; 1-(carboxymethyl) trimethylammonium chloride hydrazide; 2,2,2-trifluoroethanol; 2,2′-azobis(2-amidinopropane) dihydrochloride; 2,4-dinitrophenylhydrazine; 2-(N,N-dimethyl-amino) ethyl acrylate; 2-MeTHF; 2-acrylamino-2-methyl-propanesulfonic acid; 2-hydrazino-1-methyl-pyridine; 2-hydrazinopyridine; 2-methyltetrahydrofuran; 2-nitro-4-trifluoromethylphenylhydrazine; 2-nitrobenzaldehyde; 2NFP-APB; 4-(1H-pyrazol-1-yl) benzenesulfonyl; 4-(2-((4-bromophenethyl) dimethylammonio) ethoxy) benzenaminium dibromide; 4-(4-methyl-1-piperazyl)-3-nitrobenzoyl azide; 4-(4-nitrophenyl)-1,2,4-triazoline-3,5-dione; 4-(trimethylammonium) anilyl-N-hydroxysuccidimidyl carbamate iodide; 4-APEBA; 4-[2-(6,7-dimethoxy-4-methyl-3-oxo-3,4-dihydroquinoxalyl)ethyl]-1,2,4-triazoline-3,5-dione; 4-[2-(N,N-dimethylamino) ethylaminosulfonyl]-7-(2-aminoethylamino)-2,1,3-benzoxadiazole; 4-[2-(N,N-dimethylamino) ethylaminosulfonyl]-7-N-methylhydrazino-2,1,3-benzoxadiazole; 4-[4-(6-methoxy-2-benzoxazolyl) phenyl]-1,2,4-triazoline-3,5-dione; 4-bromomethyl-7-methoxycoumarin; 4-nitro-7-piperazion-2,1,3-benzoxadiazole; 7-chloro-4-nitro-2,1,3-benzoxadiazole; 7-fluoro-4-nitro-2,1,3-benzoxadiazole; AAPH; ACN; AIBN; AMDSA; APCI; API; APPI; APZ; BMC; CHEFOG; CID; Characterization; DAABD-AE; DAABD-MHz; DAPB; DBA; DCU; DFT; DIPEA; DMAE; DMAP; DMEQTAD; DMF; DMIS; DMSO; DNPH; DPs; Da; Dalton; Degradation products; Dns-Cl; Dns-Hz; ESI; ESI-MS; ESI-MS/TOF; FT-ICR; GirP; GirT; H/D; HILIC; HMP; HP; HPLC; HRMS; IHD; IMPs; IR; IUPAC; Impurities; International Union of Pure and Applied Chemistry; LC; LC-ESI-MS; LC–MS; LOQ; MBOTAD; MDMAES; MNBDH; MS; MS(n); MS-TOF; N-methyl-4-hydrazino-7-nitrobenzofurazan; NA; NBA; NBD-Cl; NBD-F; NBDPZ; NFPH; NH(4)OH; NIT; NMR; NPTAD; NSAIDs; PABA; PAHs; PBS; PFB-Br; PFPA; PGF2α; PPZ; PS; Practical aspects; Q-TOF; RDB; RP-HPLC; S-pentafluorophenyl tris(2,4,6-trimethoxyphenyl) phosphonium acetate bromide; SRM; Strategy; TFA; TFE; THAS; THF; TMAE; TMPP; TMPP-AcPFP; TMPP-PrG; TOF; TSH; UV; X-ray Diffraction; XRD; [3-(2-nitro-4-trifluoromethylphenyl) aminophenyl] dihydroxyborane; [M+H](+); acetonitrile; ammonium hydroxide; atmospheric pressure chemical ionization; atmospheric pressure ionization; atmospheric pressure photoionization; azobisisobutyronitrile; chemical formula generator; collision-induced dissociation; dansyl chloride; dansyl hydrazine; dansyl-3-aminophenylboronic acid; degradation products; density functional theory; di-n-butyl amine; dicyclohexyl urea; diisopropylethylamine; dimethyl amino pyridine; dimethyl sulfoxide; dimethylformamide; electrospray ionization; electrospray ionization mass spectrometry/time of flight; electrospray ionization-mass spectrometry; fourier transform-ion cyclotron resonance; high performance liquid chromatography; high resolution mass spectrometry; hydrogen/deuterium; hydrophilic interaction liquid chromatography; impurities; index of hydrogen deficiency; infrared; isonicotinoyl azide; limit of quantification; liquid chromatography; liquid chromatography-electrospray ionization-mass spectrometry; liquid chromatography–mass spectrometry; mM; mass spectrometry; mass spectrometry-time of flight; milli mass unit; millimolar; mmu; molecular ion; mono(dimethylaminoethyl) succinyl imidazolide; multi stage mass spectrometry; naphthylisothiocyanate; non-steroidal anti-inflammatory drugs; nuclear magnetic resonance; p-toluenesulfonylhydrazide; para-amino benzoic acid; parts per million; pentafluorobenzyl bromide; pentafluoropropionic acid anhydride; polycyclic aromatic hydrocarbons; ppm; prostaglandin F2α; pyridine-3-sulfonyl; quadrupole-time of flight; reversed phase-high performance liquid chromatography; ring plus double bonds; selected reaction monitoring; tetrahydrofuran; time of flight; trifluoroacetic acid; trimethyl amino-ethylalcohol; tris(2,4,6-trimethoxyphenyl) phosphine; ultra violet