The search for more versatile, sensitive, and robust ionization methods is a recurring theme in mass spectrometry (MS). Since the discovery of electrospray ionization (ESI) [1] and matrix-assisted laser desorption/ionization (MALDI), [2] many developments such as atmospheric pressure MALDI, [3] nanospray ionization, [4] Venturi-assisted electrospray, [5] and ion-funnel atmospheric pressure interfaces, [6] have paved the way to improved characterization of small molecules and biomolecules. One of the bottlenecks in achieving high sample throughput with both ESI and MALDI is the need to dissolve, extract, and/or filter the sample prior to analysis. Moreover, vacuum-incompatible materials cannot be easily investigated by MS without disturbing their innate structure. Recently, two novel methods for the direct ionization of solid samples under atmospheric pressure by MS were reported: desorption electrospray ionization (DESI) [7] and direct analysis in real time (DART). [8] More recently, McEwen et al. described a modified atmospheric pressure chemical ionization (APCI) technique for the direct analysis of solids which they named atmospheric pressure solids analysis probe (ASAP).[9] DESI makes use of a high-speed liquid spray directed at a sample held or deposited on a surface at atmospheric pressure. Ions generated during this process are sampled by a mass spectrometer. Several DESI applications such as the mapping of analytes separated by thin-layer chromatography, [10] the detection of explosives, [11,12] and the screening of pharmaceutical tablets [13][14][15] and illicit drugs [16,17] quickly followed the proof-of-principle description of the method.DART involves an ionizing beam of metastable He atoms ( 3 S 1 , 19.8 eV) generated by a corona discharge. The DART ionization mechanism is still not completely understood. In negative ion mode, the metastable He atoms generate electrons that produce negatively charged oxygen-water clusters, which then form the corresponding adducts. In positive ion mode, metastable He atoms generate protonated gaseous water clusters by Penning ionization.[8] Then, by proton exchange, these clusters form [M+H] + ions, which are generally the predominant species. DART's high throughput coupled with the high mass accuracy now attainable with modern time-of-flight mass (TOF) analyzers and accurate isotopic abundance measurements make it especially suitable for the rapid identification of unknown species in solid materials. One particularly relevant example is counterfeit drug samples. Counterfeit drugs are defined as those that are "deliberately and fraudulently mislabeled with respect to identity and/or source".[18] They may include products with the "wrong" ingredient(s), without active ingredient(s), or with an insufficient amount of active ingredient(s).In recent years, a particularly alarming case of drug counterfeiting has been reported by field researchers [19,20] who have detected counterfeit products that mimic the vital antimalarial, artesunate.[21] The consumption of fake ant...
Background: Counterfeit oral artesunate has been a major public health problem in mainland SE Asia, impeding malaria control. A countrywide stratified random survey was performed to determine the availability and quality of oral artesunate in pharmacies and outlets (shops selling medicines) in the Lao PDR (Laos).
In 2003, a stratified random sample survey was conducted in the Lao People's Democratic Republic (Laos) to study the availability and quality of antimalarials in the private sector. In 2012, this survey was repeated to allow a statistically valid analysis of change through time. The counterfeit detection device 3 (CD-3) was used to assess packaging quality in the field and HPLC and mass spectroscopy analysis chemical analysis performed. The availability of oral artesunate monotherapies had significantly decreased from 22.9% (22) of 96 outlets in southern Laos in 2003 to 4.8% (7) of 144 outlets in 2012 (P < 0.0001). All the samples collected in the 2012 survey contained the correct active pharmaceutical ingredients (APIs) in contrast to the 21 (84%) falsified artesunate samples found in the 2003 survey. Although none of the medicines found in 2012 survey had evidence for falsification, 25.4% (37) of the samples were outside the 90–110% pharmacopeial limits of the label claim, suggesting that they were substandard or degraded. Results obtained from this survey show that patients are still exposed to poorly manufactured drugs or to ineffective medicines such as chloroquine. The quality of artemisinin-based combination therapies (ACTs) used in Laos needs to be monitored, since falsified ACTs would have devastating consequences in public health.
The use of drugs in Laos was not fully appropriate in terms of rationally prescribing and dispensing practices. Since prescriptions for AB, injections, non-ED, and non-generics are still high, information on drug use provided is insufficient. Therefore, continuous health education programs among both health staff and public are needed.
Objectives In 2012, a stratified random survey, using mystery shoppers, was conducted to investigate the availability and quality of antibiotics sold to patients in the private sector in five southern provinces of the Lao People’s Democratic Republic (Laos). Methods A total of 147 outlets were sampled in 10 districts. The active pharmaceutical ingredient (API) content measurements for 909 samples, including nine APIs (amoxicillin, ampicillin, ceftriaxone, ciprofloxacin, doxycycline, ofloxacin, sulfamethoxazole, tetracycline and trimethoprim), were determined using HPLC. Results All the analysed samples contained the stated API and we found no evidence for falsification. All except one sample had all the units tested with %API values between 75% and 125% of the content stated on the label. However, we identified the presence of substandard antibiotics: 19.6% (201/1025) of samples had their units outside the 90%–110% content of the label claim and 60.2% (617/1025) of the samples had units outside of the International Pharmacopoeia uniformity of content limit range. Amoxicillin had a high number of samples [67.1% (151)] with units above the limit range, followed by ciprofloxacin [58.8% (10)] and ofloxacin [57.4% (39)]. Ceftriaxone, trimethoprim and sulfamethoxazole had the highest number of samples with low API content: 57.1% (4), 51.6% (64) and 34.7% (43), respectively. Significant differences in %API were found between stated countries of manufacture and stated manufacturers. Conclusions With the global threat of antimicrobial resistance to patient outcomes, greater understanding of the role of poor-quality antibiotics is needed. Substandard antibiotics will have reduced therapeutic efficacy, impacting public health and control of bacterial infections.
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