Fluorocarbon Plasma Gas Passivation Enhances Performance of Porous Silicon for Desorption/Ionization Mass Spectrometry.

Desorption/ionization on porous silicon mass spectrometry (DIOS-MS) is shown to be a powerful technique for the sensing of low-molecular-weight compounds, including drugs and their metabolites. Surface modification of DIOS surfaces is required to increase analytical performance and ensure stability. However, common wet chemical modification techniques use fluorosilanes, which are less suitable for high-throughput manufacturing and analytical repeatability. Here, we report an alternative, rapid functionalization technique for DIOS surfaces using plasma polymerization (ppDIOS). We demonstrate the detection of drugs, metabolites, pesticides, and doping agents, directly from biological matrices, with molecular confirmation performed using the fragmentation capabilities of a tandem MS instrument. Furthermore, the ppDIOS surfaces were found to be stable over a 162 day period with no loss of reproducibility and sensitivity. This alternative functionalization technique is cost-effective and amenable to upscaling, ensuring avenues for the high-throughput manufacture and detection of hundreds of analytes across various applications while still maintaining the gold-standard clinical technique using mass spectrometry.

Rapid Detection of Anabolic and Narcotic Doping Agents in Saliva and Urine By Means of Nanostructured Silicon SALDI Mass Spectrometry.

Novel doping agents and doping strategies are continually entering the market, placing a burden on analytical methods to detect, adapt, and respond to subtle changes in the composition of biological samples. Therefore, there is a growing interest in rapid, adaptable, and ideally confirmatory analytical methods for the fight against doping. Nanostructured silicon (nano-Si)-based surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) can effectively address this need, allowing fast and sensitive detection of prohibited compounds used in sport doping. Here, we demonstrate the detection of growth hormone peptides, anabolic-androgenic steroids, and narcotics at low concentrations directly from biological matrices. Molecular confirmation was performed using the fragmentation data of the structures, obtained with the tandem mass spectrometry capabilities of the SALDI instrument. The obtained data were in excellent agreement with those obtained using leading triple quadrupole liquid chromatography-mass spectrometry instruments. Furthermore, nano-Si SALDI-MS has the capacity for high-throughput analysis of hundreds of biological samples, providing opportunities for real-time MS analysis at sporting events.

Temperature stability of oxytocin ampoules labelled for storage at 2°C-8°C and below 25°C: an observational assessment under controlled accelerated and temperature cycling conditions.

INTRODUCTION: Oxytocin, administered via injection, is recommended by WHO for the prevention and treatment of postpartum haemorrhage. However, the susceptibility of oxytocin injection to thermal degradation has led WHO and UNICEF to recommend cold-chain storage of all oxytocin products. Nevertheless, some oxytocin products supplied to the global market are labelled for storage at ≤25°C, often with a shorter shelf-life relative to products labelled for refrigeration. Differences in labelled storage requirements can lead to uncertainties among stakeholders around the relative stability of oxytocin products and specifically whether ≤25°C products are more resistant to degradation. Such confusion can potentially influence policies associated with procurement, distribution, storage and the use of oxytocin in resource-poor settings. OBJECTIVES: To compare the stability of oxytocin injection ampoules formulated for storage at ≤25°C with those labelled for refrigerated storage. DESIGN: Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers. METHOD: Using oxytocin ampoules procured by UNFPA, accelerated stability (up to 120 days) and temperature cycling (up to 135 days between elevated and refrigerated temperatures) studies were performed at 30°C, 40°C and 50°C. Oxytocin content was quantified using a validated HPLC-UV method. RESULTS: All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for ≤25°C storage, where the rate of degradation increased at 50°C relative to other formulations. Similar degradation trends at elevated temperatures were observed during temperature cycling, while no significant degradation was observed during refrigerated periods of the study. CONCLUSION: Oxytocin ampoules formulated for non-refrigerated storage demonstrated comparable stability to those labelled for refrigerated storage and should not be interpreted by stakeholders as offering a more stable alternative. Furthermore, these products should not be procured for use in territories with high ambient temperatures, where all oxytocin injection products should be supplied and stored under refrigerated conditions.

Quality of oxytocin ampoules available in health care facilities in the Democratic Republic of Congo: an exploratory study in five provinces.

BACKGROUND: Oxytocin injection is the first line therapy for the prevention and treatment of postpartum haemorrhage (PPH), the leading cause of maternal mortality. Currently access to high quality oxytocin in low and middle-income countries (LMICs) is compromised by variable manufacturing quality and the requirement for cold chain supply and storage to prevent product deterioration. Previous studies of oxytocin ampoules sampled from Africa, the region with highest maternal mortality rates, indicate that over half do not contain the specified amount of oxytocin. International efforts continue to further understand the issues relating to oxytocin quality in LMICs and this study is the first to assess oxytocin quality in the Democratic Republic of Congo (DRC), a country that bears one of the highest global rates of maternal mortality (693 maternal deaths per 100 000 live births). Importantly, the study methodology includes the use of investigative analytical techniques to understand the cause of quality deficiencies and inform remedial measures. METHODS: The study involved sampling of oxytocin injection ampoules from public and private health care facilities (n = 15) in urban and rural areas within five provinces of the DRC. Where available, each sample comprised 20 ampoules of oxytocin injection (10 IU/mL) with smaller numbers collected where supplies were limited. Sample collection used overt sampling and mystery shopper approaches, as appropriate. Analysis of ampoules for oxytocin content and known degradation products utilised validated HPLC and LCMS methods, respectively. Sterility testing was conducted in accordance with the United States Pharmacopeia monograph. RESULTS: Eighty percent of ampoules collected contained less than 90% of the specified content. Known degradation products of oxytocin were identified, indicating likely exposure to elevated temperatures post-manufacture. All samples contained an unknown impurity at a level of approximately 12.3% (8.0-20.5%) of the oxytocin main band peak. No samples failed sterility testing. CONCLUSIONS: There is evidence of a high prevalence of poor quality oxytocin ampoules in health facilities in the DRC likely resulting from both manufacturing quality issues and uncontrolled storage. A more comprehensive post-marketing surveillance study of oxytocin quality is warranted.