Direct monitoring of drug degradation by easy ambient sonic-spray ionization mass spectrometry: the case of enalapril

Abstract

Using enalapril maleate as a test case, the ability of ambient mass spectrometry, namely, via easy ambient sonic-spray ionization mass spectrometry (EASI-MS), to perform direct monitoring of drug degradation has been tested. Two manufacturing processes were investigated (direct compression and wet granulation), and the formation of degradation products was measured via both EASI-MS and high-performance liquid chromatography with ultraviolet detection for a total period of 18 months. Both techniques provide comparable results, which indicate that direct analysis by ambient mass spectrometric techniques presents a viable alternative for drug degradation monitoring with superior simplicity, throughput, and reliability (no sample manipulation), and comparable quantitative results. In terms of qualitative monitoring, the full mass spectra with intact species provided by EASI-MS allow for comprehensive monitoring of known and unknown (or unexpected) degradation products.

A dopant for improved sensitivity in easy ambient sonic‐spray ionization mass spectrometry

“…Pure methanol and methanol with 10 ppm of 3‐NBN were therefore compared as the solvent for EASI‐MS analysis of biodiesel, olive oil and the prednisone drug. These samples were selected as test cases because they have been among the most typical samples tested for EASI‐MS …”

“…Pure methanol and methanol with 10 ppm of 3-NBN were therefore compared as the solvent for EASI-MS analysis of biodiesel, olive oil and the prednisone drug. These samples were selected as test cases because they have been among the most typical samples tested for EASI-MS. [15,28,29] Biodiesel Figure 3 shows EASI(+)-MS of a single droplet of a soybean biodiesel sample performed using pure methanol or methanol doped with 10 ppm of 3-NBN. Note that as reported before, [28,30] the major fatty acids methyl esters (FAME) of soybean biodiesel are detected by EASI-MS as the sodiated molecules [M + Na] + in which that from linoleic acid (m/z 317) dominates.…”

LC-MS characterization of valsartan degradation products and comparison with LC-PDA

“…Interestingly, the MS study of the fragmentation pattern of gaseous drugs in protonated, deprotonated and ionized forms has been found to match or provide insights on their degradation mechanisms and products (Amaral et al, 2011). The fragmentation patterns of gaseous molecules reveal the weaker molecule bonds; hence, some of the fragment ions may eventually match degradation products, particularly when the behavior of a protonated molecule is compared to that expected under acid stress condition.…”

“…At present, direct MS analysis approaches using soft ionization methods applied to drug pills have been reported and may also be suitable for some drugs (Amaral et al, 2011).…”

Mass spectrometry made easy: The quest for simplicity

“…EASI and its sister techniques have been used in a variety of applications; for (1) the direct analysis of drug, pills as exemplified for sildenafil (Figure a), and for the characterization of TLC spots, as exemplified for cocaine (Figure b), for the quality control and certification of geographical origin of olive oils; for direct fingerprinting control of forgery in perfumes; for the nearly instantaneous characterization of the composition of cationic surfactants and quality control of fabric softeners; for the analysis of biodiesel and biodiesel/petrodiesel blends in combination with high performance thin layer chromatography; for fingerprinting analysis of propolis; for the direct analysis of fuels; for the instantaneous characterization of vegetable oils via TAG and FFA profiles, in combination with selective sequesters based on molecularly imprinted polymers (MIP) for the analysis of phenothiazines in urine (Figure d); for the fingerprinting and aging of ink in forensic investigations; as a rapid and secure screening method for street illegal drugs; to characterize noble and endangered woods; for the direct monitoring of known and unknown (or unexpected) drug degradation products as a function of time and manufacturing process, as exemplified for enalapril maleate (Figure c), via thermal imprinting for the analysis of TAG profiles in meat matrices; for petroleomic studies of ‘untouched’ crude oil samples; for the forensic investigation of counterfeit money bills; and, in its Venturi version, for real‐time analysis of brain tissue . These are illustrative of the ‘whole world’ (see cover picture) application of modern ‘simpler’ MS.…”