Stability and Degradation Pathways of Different Psychoactive Drugs in Neat and in Buffered Oral Fluid

Abstract Sampling and drug stability in oral fluid (OF) are crucial factors when interpreting forensic toxicological analysis, mainly because samples may not be analyzed immediately after collection, potentially altering drug concentrations. Therefore, the stability of some common drugs of abuse (morphine, codeine, 6-monoacetylmorphine, cocaine, benzoylecgonine, Δ9-tetrahydrocannabinol, cannabidiol, amphetamine, 3,4-methylenedioxymethamphetamine, ketamine) and the more commonly consumed new psychoactive substances in our environment (mephedrone, and N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide 5F-AKB48 also known as 5F-APINACA) was investigated in an OF pool for the presence and absence of M3 Reagent Buffer® up to 1 year of storage. Fortified OF samples were stored at three different temperatures (room temperature, 4 and −20°C) to determine the best storage conditions over time. Control fortified OF samples were stored at −80°C for reference purposes. Compounds with concentration changes within ±15% of initial value were considered stable. The drugs were significantly more stable in M3 Reagent Buffer® than in neat OF samples in all storage conditions. All analytes were stable for 1 year at 4°C and −20°C in M3 Reagent Buffer®. Drugs stability in OF varied depending on the analyte, the presence of a stabilizer, the storage duration and temperature. When immediate sample analysis is not possible, we suggest to store OF samples at 4 or −20°C and test them within 2 weeks. Alternatively, OF samples may be stored at 4 or −20°C with M3 Reagent Buffer® to be tested within 1 year.

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Screening of 104 New Psychoactive Substances (NPS) and Other Drugs of Abuse in Oral Fluid by LC–MS-MS

Journal of Analytical Toxicology ◽

10.1093/jat/bkaa089 ◽

2020 ◽

Vol 44 (7) ◽

pp. 697-707

Author(s):

Kelly Francisco da Cunha ◽

Karina Diniz Oliveira ◽

Marilyn A Huestis ◽

Jose Luiz Costa

Keyword(s):

Oral Fluid ◽

Drugs Of Abuse ◽

Matrix Effects ◽

Synthetic Cannabinoids ◽

Screening Method ◽

Simultaneous Detection ◽

New Psychoactive Substances ◽

Major Public Health Problem ◽

Psychoactive Substances ◽

Wide Range

Abstract New psychoactive substances (NPS) are a major public health problem, primarily due to the increased number of acute poisoning cases. Detection of these substances is a challenge. The aim of this research was to develop and validate a sensitive screening method for 104 drugs of abuse, including synthetic cannabinoids, synthetic cathinones, fentanyl analogues, phenethylamines and other abused psychoactive compounds (i.e., THC, MDMA, LSD and their metabolites) in oral fluid by liquid chromatography–tandem mass spectrometry (LC–MS-MS). The Quantisal™ oral fluid device was used to collect oral fluid samples. The oral fluid–elution buffer mixture (500-μL sample) was extracted with t-butyl methyl ether, and chromatographic separation was performed on a Raptor™ biphenyl column (100 × 2.1 mm ID, 2.7 μm), with a total run time of 13.5 min. Limits of detection were established at three concentrations (0.05, 0.1 or 1 ng/mL) for most analytes, except for acetyl norfentanyl and mescaline (5 ng/mL). Matrix effects were generally <20% and overall extraction recoveries >60%. The highest matrix effect was observed within the synthetic cannabinoid group (PB22, −55.5%). Lower recoveries were observed for 2C-T (47.2%) and JWH-175 (58.7%). Recoveries from the Quantisal™ device were also evaluated for all analytes (56.7–127%), with lower recoveries noted for 25I-NBOMe, valerylfentanyl and mCPP (56.7, 63.0 and 69.9%, respectively). Drug stability in oral fluid was evaluated at 15, 60 and 90 days and at 25, 4 and −20°C. As expected, greater stability was observed when samples were stored at −20°C, but even when frozen, some NPS (e.g., synthetic cannabinoids) showed more than 20% degradation. The method was successfully applied to the analysis of seven authentic oral fluid samples positive for 17 different analytes. The method achieved good sensitivity and simultaneous detection of a wide range of NPS.

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Replacement of immunoassay by LC tandem mass spectrometry for the routine measurement of drugs of abuse in oral fluid

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1258/0004563054255632 ◽

2005 ◽

Vol 42 (4) ◽

pp. 277-284 ◽

Cited By ~ 40

Author(s):

KR Allen ◽

R Azad ◽

HP Field ◽

DK Blake

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Oral Fluid ◽

Drugs Of Abuse ◽

Multiple Reaction Monitoring ◽

Gradient Elution ◽

Tandem Mass ◽

Drug Concentrations ◽

Wide Range ◽

The Matrix

Background: There is increasing interest in the use of oral fluid as the matrix for the detection of drugs of abuse which requires the use of sensitive immunoassays to achieve the low detection limits required. The use of liquid chromatography linked to tandem mass spectrometry (LC/MS/MS) is explored as a possible replacement for immunoassay in screening for drugs of abuse in oral fluid samples. Methods: Oral fluid samples collected from 72 subjects attending an addiction clinic were screened for opiates, cocaine, methadone and benzodiazepines using both enzyme-linked immunosorbent assays (ELISA) and LC/MS/MS. The latter analysis used a short gradient elution with individual drugs detected by multiple reaction monitoring using tandem mass spectrometry. Results between the two methods were compared qualitatively using the cut-off concentrations defined by the ELISA assays. Results: With regard to the ELISA assays which show group specificity, LC/MS/ MS detected the presence of 6-monoacetylmorphine, morphine or dihydrocodeine in all but two of 49 samples positive for opiates. Of 55 samples positive for benzodiazepines by ELISA, all but two were confirmed by LC/MS/MS. Overall, LC/MS/MS compared favourably with ELISA for detection of specific drugs or their metabolites in the case of morphine, methadone and the cocaine metabolite benzoylecgonine. Many of the discrepant results between the two assays were a result of samples with drug concentrations near to the cut-off concentrations and the imprecision of these assays at very low concentrations. Conclusion: LC/MS/MS offers a more flexible, specific and sensitive alternative to the screening of oral fluid samples for drugs of abuse than ELISA. A wide range of drugs and metabolites can be detected from a single sample injection.

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Using biological samples in epidemiological research on drugs of abuse

Norsk Epidemiologi ◽

10.5324/nje.v21i1.1420 ◽

2011 ◽

Vol 21 (1) ◽

Cited By ~ 14

Author(s):

Hallvard Gjerde ◽

Elisabeth Leere Øiestad ◽

Asbjørg S. Christophersen

Keyword(s):

Drug Use ◽

Drug Testing ◽

Oral Fluid ◽

Drugs Of Abuse ◽

Drug Dose ◽

Biological Matrices ◽

Single Drug ◽

Drug Concentrations ◽

Frequency Of Use ◽

Hair Samples

Blood, oral fluid (saliva), urine and hair are the most commonly used biological matrices for drug testing in epidemiological drug research. Other biological matrices may also be used for selected purposes. Blood reflects recent drug intake and may be used to assess impairment. Oral fluid reflects drug presence in blood and thereby also recent intake, but drug concentrations in this matrix cannot be used to accurately estimate concentrations in blood. Urine reflects drug use during the last few days and in some cases for a longer period, but does not indicate the dose size or frequency of use. Hair reflects drug use during several months, but is a poor matrix for detecting use of cannabis. If using a single drug dose, this can be detected in blood and urine if the sample is taken within the detection timeframes, in most cases also in oral fluid. Single drug use is most often insufficient for producing a positive test result in a sample of hair. For cocaine and amphetamine, weekly use may be needed, while for cannabis a positive result is not guaranteed even after daily use. Refusal rates are lowest for oral fluid and highest for blood and hair samples. The analytical costs are lowest for urine and highest for hair. Combined use of questionnaires/interviews and drug testing detects more drug use than when using only one of those methods and is therefore expected to give more accurate data.

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A Novel Stability Study of Simvastatin Generic Tablet in Public Pharmacy Facilities of Purwakarta District, Indonesia

INDONESIAN JOURNAL OF PHARMACY ◽

10.22146/ijp.2730 ◽

2021 ◽

pp. 548-562

Author(s):

Muchtaridi Muchtaridi ◽

Rini Yulianita ◽

Iyan Sopyan ◽

Amirah Mohd Gazzali

Keyword(s):

Drug Stability ◽

Stress Test ◽

Simulation Method ◽

Storage Conditions ◽

Quality Parameters ◽

Stability Study ◽

Storage Duration ◽

Disintegration Time ◽

Temperature And Humidity ◽

Physical And Chemical Quality

Drug stability is one of the most important criteria for producing safe, excellent and effective products. Some environmental factors that influence drug stability are light, temperature, and humidity. Simvastatin is a cholesterol-lowering drug that is known to be sensitive to high temperature and humidity. The purpose of this study is to analyze the effect of 6 months of real-time storage conditions on the stability of generic simvastatin tablets in public pharmacy facilities. This study used simulation method with 4 brands of simvastatin generic tablets with two different strengths (10 mg and 20 mg). In the process, the sample was conditioned in 6 different regions for 6 months. The results of temperature and humidity monitoring showed 2 locations at ≤ 25 ° C, 4 locations had a temperature of ≥ 25 °C and all locations had humidity > 65 %. The drug was evaluated for physical and chemical quality parameters at months 0, 3, and 6. After being stored for 6 months, the tablets showed a decrease in disintegration time and an increase in the friability, showing lack of durability. Similarly, there was a decrease in the content concentration in the tablets but fortunately the level was still within the accepted specification range (90 – 110 %). However, there was one tablet that did not meet the dissolution test requirements after the storage duration (Q ≤ 75 % at 30 minutes). The results of the stress test showed that simvastatin degraded in all conditions. This stress test confirmed the extreme instability of simvastatin. Poor storage conditions can reduce the quality of generic simvastatin tablets, thus a well-controlled environment is vital in pharmacy facilities.

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Effects of Storage Duration on Biodiesel Properties Derived from Waste Cooking Oil

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.554.494 ◽

2014 ◽

Vol 554 ◽

pp. 494-499 ◽

Cited By ~ 19

Author(s):

Amir Khalid ◽

Norazwan Azman ◽

Hanis Zakaria ◽

Bukhari Manshoor ◽

Izzuddin Zaman ◽

...

Keyword(s):

Water Content ◽

Fossil Fuels ◽

Storage Temperature ◽

Acid Value ◽

Waste Cooking Oil ◽

Storage Conditions ◽

Storage Duration ◽

Oil Reserves ◽

Cooking Oil ◽

Different Temperatures

The reduction of world oil reserves fossil fuels and increasing environmental concerns significantly influences the popularity of biodiesel as an alternative diesel. This research investigates the effects of storage duration of variant blending waste cooking oil ratio under different storage temperature on fuel properties. The biodiesel samples were stored at different temperatures and were monitored at regular interval over a period of 70 days. Blending of biodiesel was varied from 5vol % (WCO5) ~15vol% (WCO15) and storage temperature from 24°C~35°C. These samples were monitored on a weekly and the effects of storage conditions on properties of biodiesel such as density, kinematics viscosity, acid value, water content and flash point of biodiesel were discussed in detail. The observation of biodiesel shows that the increasing of storage duration of biodiesel derived from waste cocking oil influences to the increasing of density, kinematics viscosity, acid value and water content.

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Determination and Improvement of the Postharvest Storability of Little Mallow (Malva Parviflora L.): A Novel Crop for a Sustainable Diet

HortScience ◽

10.21273/hortsci15179-20 ◽

2020 ◽

Vol 55 (8) ◽

pp. 1378-1386 ◽

Cited By ~ 1

Author(s):

İbrahim Kahramanoğlu ◽

Chunpeng Wan

Keyword(s):

Modified Atmosphere Packaging ◽

Storage Conditions ◽

Hot Water ◽

Storage Duration ◽

Suitable Heat Treatment ◽

Sustainable Diet ◽

Different Temperatures ◽

Malva Parviflora ◽

Favorable Conditions

Little mallow (Malva parviflora L.) has been traditionally used as an alternative food source. To the authors’ knowledge, there is no available published information about the postharvest storability of little mallow. This study was conducted in three steps. It aimed to determine the postharvest storability of little mallow leaves and to improve its storability using different strategies. First, the effects of four different storage conditions on the storability of little mallow leaves were tested to determine the most favorable conditions for further studies: 5 ± 1 °C and 95% relative humidity (RH); 9 ± 1 °C and 95% RH; 13 ± 1 °C and 95% RH; and 24 ± 1 °C and 55% RH as control. Preliminary experiments suggested that the best temperature and RH combination is 9 ± 1 °C and 95% RH. Hence, the effects of hot water dipping (HWD) were tested at three different temperatures (40, 45, and 50 °C) for two different durations (60 and 120 seconds); the results suggested that the 40 °C treatment is the most suitable heat treatment for improving the storability of mallow. The final experiments were conducted with 15 different treatments, including HWD, eco-friendly edible bio-materials, modified atmosphere packaging, and ultraviolet radiation. Results showed that low-density polyethylene (LDPE) (60 × 60 cm; thickness, 50 μ) and polypropylene (PP) (35 × 50 cm; thickness, 35 μ) packaging provide the highest efficacy for preserving overall quality. The edible quality of little mallow can be extended to 15 days with PP and 12 days with LDPE. However, both materials caused an abnormal odor after that time. Further studies involving additional edible coatings are necessary to determine if the storage duration of little mallow leaves could be extended.

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Postmortem Metabolomics: Strategies to Assess Time-Dependent Postmortem Changes of Diazepam, Nordiazepam, Morphine, Codeine, Mirtazapine and Citalopram

Metabolites ◽

10.3390/metabo11090643 ◽

2021 ◽

Vol 11 (9) ◽

pp. 643

Author(s):

Lana Brockbals ◽

Yannick Wartmann ◽

Dylan Mantinieks ◽

Linda Glowacki ◽

Dimitri Gerostamoulos ◽

...

Keyword(s):

Drugs Of Abuse ◽

Individual Variability ◽

Time Dependent ◽

Postmortem Changes ◽

Knowledge Gain ◽

Mixed Effect ◽

Drug Concentrations ◽

Liquid Chromatography Tandem Mass ◽

Forensic Case ◽

Concentration Changes

Postmortem redistribution (PMR) can result in artificial drug concentration changes following death and complicate forensic case interpretation. Currently, no accurate methods for PMR prediction exist. Hence, alternative strategies were developed investigating the time-dependent postmortem behavior of diazepam, nordiazepam, morphine, codeine, mirtazapine and citalopram. For 477 authentic postmortem cases, femoral blood samples were collected at two postmortem time-points. All samples were quantified for drugs of abuse (targeted; liquid chromatography-tandem mass spectrometry LC-MS/MS) and characterized for small endogenous molecules (untargeted; gas chromatography-high resolution MS (GC-HRMS). Trends for significant time-dependent concentration decreases (diazepam (n = 137), nordiazepam (n = 126)), increases (mirtazapine (n = 55), citalopram (n = 50)) or minimal median postmortem changes (morphine (n = 122), codeine (n = 92)) could be observed. Robust mathematical mixed effect models were created for the generalized postmortem behavior of diazepam and nordiazepam, which could be used to back-calculate drug concentrations towards a time-point closer to the estimated time of death (caution: inter-individual variability). Significant correlations between time-dependent concentration changes of morphine, mirtazapine and citalopram with individual endogenous molecules could be determined; no correlation was deemed strong enough for successful a posteriori estimation on the occurrence of PMR for specific cases. The current dataset did successfully lead to a significant knowledge gain in further understanding the time-dependent postmortem behavior of the studied drugs (of abuse).

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Changes of Physicochemical Properties of Starch Syrups Recommended for Winter Feeding of Honeybees during Storage

Agriculture ◽

10.3390/agriculture11040374 ◽

2021 ◽

Vol 11 (4) ◽

pp. 374

Author(s):

Teresa Szczęsna ◽

Ewa Waś ◽

Piotr Semkiw ◽

Piotr Skubida ◽

Katarzyna Jaśkiewicz ◽

...

Keyword(s):

Chemical Composition ◽

Physicochemical Properties ◽

Physicochemical Parameters ◽

Storage Temperature ◽

Storage Conditions ◽

Different Temperatures ◽

And Storage ◽

Bee Colonies ◽

Temperature Time ◽

Winter Feeding

The aim of this study was to determine the influence of storage temperature and time on physicochemical parameters of starch syrups recommended for the winter feeding of bee colonies. The studies included commercially available three starch syrups and an inverted saccharose syrup that were stored at different temperatures: ca. 20 °C, 10–14 °C, and ca. 4 °C. Physicochemical parameters of fresh syrups (immediately after purchase) and syrups after 3, 6, 9, 12, 15, 18, 21, and 24 months of storage at the abovementioned temperatures were measured. It was observed that the rate of unfavorable changes in chemical composition of starch syrups and the inverted saccharose syrup, mainly the changes in the 5-hydroxymethylfurfural (HMF) content, depended on the type of a syrup and storage conditions (temperature, time). Properties of tested starch syrups intended for winter feeding of bees stored at ca. 20 °C maintained unchanged for up to 6 months, whereas the same syrups stored at lower temperatures (10–14 °C) maintained unchanged physicochemical parameters for about 12 months. In higher temperatures, the HMF content increased. To date, the influence of this compound on bees has not been thoroughly investigated.

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Seed longevity of maize conserved under germplasm bank conditions for up to 60 years

Annals of Botany ◽

10.1093/aob/mcab009 ◽

2021 ◽

Author(s):

Filippo Guzzon ◽

Maraeva Gianella ◽

Jose Alejandro Velazquez Juarez ◽

Cesar Sanchez Cano ◽

Denise E Costich

Keyword(s):

Seed Germination ◽

Plant Genetic Resources ◽

Seed Viability ◽

Storage Conditions ◽

Seed Longevity ◽

Germplasm Bank ◽

Significant Difference ◽

Different Temperatures ◽

Germination Experiments

Abstract Background and Aims The long-term conservation of seeds of plant genetic resources is of key importance for food security and preservation of agrobiodiversity. Nevertheless, there is scarce information available about seed longevity of many crops under germplasm bank conditions. Methods Through germination experiments as well as the analysis of historical monitoring data, we studied the decline in viability manifested by 1000 maize (Zea mays subsp. mays) seed accessions conserved for an average of 48 years at the CIMMYT germplasm bank, the largest maize seedbank in the world, under two cold storage conditions: an active (–3 °C; intended for seed distribution) and a base conservation chamber (–15 °C; for long-term conservation). Key Results Seed lots stored in the active chamber had a significantly lower and more variable seed germination, averaging 81.4 %, as compared with the seed lots conserved in the base chamber, averaging 92.1 %. The average seed viability detected in this study was higher in comparison with that found in other seed longevity studies on maize conserved under similar conditions. A significant difference was detected in seed germination and longevity estimates (e.g. p85 and p50) among accessions. Correlating seed longevity with seed traits and passport data, grain type showed the strongest correlation, with flint varieties being longer lived than floury and dent types. Conclusions The more rapid loss of seed viability detected in the active chamber suggests that the seed conservation approach, based on the storage of the same seed accessions in two chambers with different temperatures, might be counterproductive for overall long-term conservation and that base conditions should be applied in both. The significant differences detected in seed longevity among accessions underscores that different viability monitoring and regeneration intervals should be applied to groups of accessions showing different longevity profiles.

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