Disposal practices of unused and expired pharmaceuticals among general public in Kabul.

BACKGROUND: Most of the medicine users remain unaware about the disposal of unused or expired medicines. The aim of this study was to know the disposal practices of unused and expired medicines among the general public in Kabul. METHODS: This was a descriptive, cross-sectional survey, conducted through face-to-face interviews using prevalidated structured questionnaire. Returned questionnaires were double-checked for accuracy. Statistical Package for Social Science (SPSS) version 23 was used for statistical analysis. RESULTS: Total of 301 valid questionnaires were returned with a response rate of 100% in which 73.4% men and 26.6% women participated. More than half of the respondents were university graduates. Interestingly, 83.4% of the interviewees purchased medicines on the prescription of which 47.2% were university graduates, while 14.6% purchased medicine over the counter. Among the respondents, 46.5/100 purchased antibiotics and the remaining purchased NSAIDs, anti-hypertensive and anti-diabetic medicines. Significantly, 97/100 checked the expiry date of medicine before buying. Majority (95.3%) of the respondents' stored medicines at home. 77.7% of the respondents discarded the expired medicines in household trash. Majority of respondents held government responsible for creation of awareness for proper medicine disposal. Almost entire sample (98%) felt that improper disposal of unused and expired medicines can affect the environment and health. CONCLUSION: Gaps exist in practices, therefore robust, safe and cost-effective pharmaceutical waste management program supported with media campaign is needed. Healthcare practitioners and community pharmacists should offer training to educate customers on standard medicine disposal practices.

Assessment of maternal drug intake by urinary bio monitoring during pregnancy and postpartally until the third perinatal year.

PURPOSE: Although sales of prescribed and over-the-counter (OTC) medication are rising, little is known about individual drug intake. This study was aimed to obtain complementary information about drug intake. METHOD: Information on drug utilization was obtained in a female cohort for five different time points (TP): 36th week of pregnancy (n = 622), 7th perinatal week (n = 533), 3rd perinatal month (n = 340), and 1st perinatal (n = 534) and 3rd perinatal year (n = 324) by a validated urine screening method. RESULTS: Drugs were detected 807 times among all analyzed samples (n = 2353) with less drug intake for early TP compared with later TP (~24.4%, n = 152; ~33.8%, n = 180; ~23.2%, n = 79; ~42.5%, n = 227; and ~52.2%, n = 169). The diversity of drugs increased from 25 up to 40 different drugs for the investigated period. OTC drugs were detected most frequently reflected by the top three drugs: acetaminophen (~37%, n = 292), ibuprofen (~23%, n = 183), and xylometazoline (~12%, n = 98). Mainly guideline-orientated drug therapy was observed. However, contraindicated ibuprofen intake during third trimester urine samples (n = 26) and a repeated usage of acetaminophen and/or ibuprofen (n = 9), as well as xylometazoline (n = 7), reveal missing information about drug safety. CONCLUSION: Bio monitoring was applied for detection of drug intake revealing a lack of information about OTC products and their health risks. Hence, information about health risks for certain drugs and patient groups must be improved for and by pharmacists, to avoid (i) usage of contraindicated drugs and (ii) abuse of OTC drugs.

Validated multi-drug determination using liquid chromatography with tandem mass spectrometry for the evaluation of a commercial drug disposal product.

Currently, there are limited effective means of drug disposal for consumers, and this creates a gateway to illicit use and environmental contamination. Here, we evaluated the efficacy of a new drug disposal product, composed from a slurry of activated carbon, which claims to sequester up to 100% of a drug's active ingredient when the loading capacity is not exceeded, making it safe to dispose in landfill. High-performance liquid chromatography with tandem mass spectrometry was applied to quantify as many as 24 drugs (opiates, barbiturates, statins, amphetamine, and benzodiazepine drugs) in the residual solvent solution from the product. Calibration curves were established in the concentration ranges of 0.25-7.0 µg/mL and showed good linearity. The limits of detection varied from 0.001 to 0.02 µg/mL, depending on the drug. Accuracy ranged from 80 to 111% for quality control samples, with a few minor exceptions. Precision overall varied between 0.2 to 12.7%. In sample bottles tested, where active ingredient of the loaded drug was below the maximum sorption capacity stated on the label, 98 to >99.9% of the active ingredient was sequestered. Percent active ingredient adsorbed was slightly lower in bottles loaded in excess of label specifications.

Fair Balance and Adequate Provision in Direct-to-Consumer Prescription Drug Online Banner Advertisements: A Content Analysis.

BACKGROUND: The current direct-to-consumer advertising (DTCA) guidelines were developed with print, television, and radio media in mind, and there are no specific guidelines for online banner advertisements. OBJECTIVE: This study evaluates how well Internet banner ads comply with existing Food and Drug Administration (FDA) guidelines for DTCA in other media. METHODS: A content analysis was performed of 68 banner advertisements. A coding sheet was developed based on (1) FDA guidance documents for consumer-directed prescription drug advertisements and (2) previous DTCA content analyses. Specifically, the presence of a brief summary detailing the drug's risks and side effects or of a "major statement" identifying the drug's major risks, and the number and type of provisions made available to consumers for comprehensive information about the drug were coded. In addition, the criterion of "fair balance," the FDA's requirement that prescription drug ads balance information relating to the drug's risks with information relating to its benefits, was measured by numbering the benefit and risk facts identified in the ads and by examining the presentation of risk and benefit information. RESULTS: Every ad in the sample included a brief summary of risk information and at least one form of adequate provision as required by the FDA for broadcast ads that do not give audiences a brief summary of a drug's risks. No ads included a major statement. There were approximately 7.18 risk facts for every benefit fact. Most of the risks (98.85%, 1292/1307) were presented in the scroll portion of the ad, whereas most of the benefits (66.5%, 121/182) were presented in the main part of the ad. Out of 1307 risk facts, 1292 were qualitative and 15 were quantitative. Out of 182 benefit facts, 181 were qualitative and 1 was quantitative. The majority of ads showed neutral images during the disclosure of benefit and risk facts. Only 9% (6/68) of the ads displayed positive images and none displayed negative images when presenting risks facts. When benefit facts were being presented, 7% (5/68) showed only positive images. No ads showed negative images when the benefit facts were being presented. CONCLUSIONS: In the face of ambiguous regulatory guidelines for online banner promotion, drug companies appear to make an attempt to adapt to regulatory guidelines designed for traditional media. However, banner ads use various techniques of presentation to present the advertised drug in the best possible light. The FDA should formalize requirements that drug companies provide a brief summary and include multiple forms of adequate provision in banner ads.

Field study to detect illicit and medicinal drugs in car drivers in Southern and Western Hesse.

In the present study, immunochemical tests (Mahsan DrugInspector, DOA4, DOA8, DOA10, Protzek) as well as the detection rate of police checks were evaluated. Urine and blood samples of suspected car drivers were analysed by chromatography-mass spectrometry. Additionally, anonymised urine samples were analysed on a voluntary basis in cases where no legal proceedings were initiated. Toxicological analyses (total unknown screening) were performed using gas chromatography-mass spectrometry (GC-MS) after hydrolysis, acidic and alkaline extraction and derivatization. A data base for screening 9000 substance entries was applied. In addition, urine samples were analysed using liquid chromatography/ time-of-flight mass spectrometry (HPLC-ToF-MS) to screen psychiatric and narcotic drugs. In total, samples of 154 suspects were analysed, of these, 46 samples for no actual reason. In 5 of the latter samples, forensically relevant substances were detected; in two cases the consumption of illicit drugs, i. e. cannabis and methamphetamine, was proved. Of the 154 suspects, 108 were charged with driving under the influence of drugs; in samples of 103 of these cases, illicit drugs were found. Immunochemical pretesting showed posi- tive results in 97 of the 108 cases; in 6 samples, psychiatric drugs (citalopram, doxepin, promethazine, mirtazapine, fluoxetine, venlafaxine) were later identified, which are not detectable by ordinary pretesting systems. Police officers successfully identified 95.4 % of the suspects as drug consumers, which is an excellent result. In practice, pretesting of urine samples using immunochemical techniques proved to be very reliable. The Protzek system in particular corresponded well with the results of the chromatographic analyses. In conclusion, systematic chromatographic-mass spectrometric analysis of urine samples of suspects is recommended to identify car drivers consuming illicit drugs and to obtain data usable in legal proceedings (e. g. suspending of the driving license), which is not always possible when using blood samples in cases of drugs consumed some time ago.

Levels and potential health risks of mercury in prescription, non-prescription medicines and dietary supplements in Poland.

Determination of mercury is important in the case of pharmaceuticals for which the European Union regulations have not defined the maximum permissible concentration of this metal. The aim of the study was to determine the levels of mercury in the following groups of drugs (n = 119): analgesics, diuretics, cardiacs, antihypertensives, anti-influenza, antibiotics, anti-allergics, tranquilizers, antibacterials and in dietary supplements (n = 33) available on the Polish market. Mercury was analyzed using cold vapor atomic fluorescence spectrometry CV-AFS. Its content in the samples varied in the range of 0.9-476.1 ng g(-1). Higher mercury concentrations were reported for prescription drugs (Rx): 0.9-476.1 ng g(-1) (median: 7.4 ng g(-1)), lower--for non-prescription medicines (OTC): 1.2-45.8 ng g(-1) (median: 6.0 ng g(-1)). In the analyzed dietary supplements the concentrations were: 0.9-16.7 ng g(-1) (median: 5.9 ng g(-1)). On the basis of the information contained in the leaflet accompanying the medicine, a daily dose of mercury taken into the body with an analyzed medicament was estimated and the health risk posed by using such medicines was assessed. The study indicates that it is justified to carry out measurements of mercury in pharmaceuticals due to its high, potentially harmful.

Desorption electrospray ionization (DESI) with atmospheric pressure ion mobility spectrometry for drug detection.

Desorption electrospray ionization (DESI) was coupled to an ambient pressure drift tube ion mobility time-of-flight mass spectrometer (IM-TOFMS) for the direct analysis of active ingredients in pharmaceutical samples. The DESI source was also coupled with a standalone IMS demonstrating potential of portable and inexpensive drug-quality testing platforms. The DESI-IMS required no sample pretreatment as ions were generated directly from tablets and cream formulations. The analysis of a range of over-the-counter and prescription tablet formations was demonstrated for amphetamine (methylphenidate), antidepressant (venlafaxine), barbiturate (Barbituric acid), depressant (alprazolam), narcotic (3-methylmorphine) and sympatholytic (propranolol) drugs. Active ingredients from soft and liquid formulations, such as Icy Hot cream (methyl salicylate) and Nyquil cold medicine (acetaminophen, dextromethorphan, doxylamine) were also detected. Increased sensitivity for selective drug responses was demonstrated through the formation of sodiated adduct ions by introducing small quantities of NaCl into the DESI solvent. Of the drugs and pharmaceuticals tested in this study, 68% (22 total samples) provided a clear ion mobility response at characteristic mobilities either as (M + H)(+), (M - H)(-), or (M + Na)(+) ions.

Determination of drugs and drug-like compounds in different samples with direct analysis in real time mass spectrometry.

Direct analysis in real time (DART), a relatively new ionization source for mass spectrometry, ionizes small-molecule components from different kinds of samples without any sample preparation and chromatographic separation. The current paper reviews the published data available on the determination of drugs and drug-like compounds in different matrices with DART-MS, including identification and quantitation issues. Parameters that affect ionization efficiency and mass spectra composition are also discussed.

Direct, metal-free amination of heterocyclic amides/ureas with NH-heterocycles and N-substituted anilines in POCl3.

A POCl(3)-mediated, direct amination reaction of heterocyclic amides/ureas with NH-heterocycles or N-substituted anilines is described. Compared to the existing methods, this operationally simple protocol provides unique reactivity and functional group compatibility because of the metal-free, acidic reaction conditions. The yields are generally excellent.

A multivariate chemical similarity approach to search for drugs of potential environmental concern.

A structural similarity tool was developed and aimed to search for environmentally persistent drugs. The basis for the tool was a selection of so-called anchor molecules and a multidimensional chemical map of drugs. The map was constructed using principal component analysis covering 899 drugs described by 67 diverse calculated chemical descriptors. The anchor molecules (diclofenac, trimethoprim, and carbamazepine) were selected to represent drugs of known environmental concern. In addition 12 chemicals listed by the Stockholm Convention on persistent organic pollutants were used representing typical environmental pollutants. Chemical similarity was quantified by measuring relative Euclidean distances in the five-dimensional chemical map, and more than 100 nearest neighbors (kNNs) were found within a relative distance of less than 10% from each drug anchor. The developed chemical similarity approach not only identified persistent or semipersistent drugs but also a large number of potentially persistent drugs lacking environmental fate data.

Use of proton transfer reaction time-of-flight mass spectrometry for the analytical detection of illicit and controlled prescription drugs at room temperature via direct headspace sampling.

The first reported use of proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS) for the detection of a range of illicit and prescribed drugs is presented here. We describe the capabilities of PTR-TOF-MS to detect the following commonly used narcotics-ecstasy (N-methyl-3,4-methylenedioxyamphetamine), morphine, codeine, cocaine and heroin-by the direct sampling of the headspace above small solid quantities (approximately 50 mg) of the drugs placed in glass vials at room temperature, i.e. with no heating of the sample and no pre-concentration. We demonstrate in this paper the ability to identify the drugs, both illicit and prescribed, using PTR-TOF-MS through the accurate m/z assignment of the protonated parent molecule to the second decimal place. We have also included in this study measurements with an impure sample of heroin, containing typical substances found in "street" heroin, to illustrate the use of the technology for more "real-world" samples. Therefore, in a real-world complex chemical environment, a high level of confidence can be placed on the detection of drugs. Although the protonated parent is observed for all drugs, the reactant channel leading to this species is not the only one observed and neither is it necessarily the most dominant. Details on the observed fragmentation behaviour are discussed and compared to electrospray ionisation MS(n) studies available in the literature.

Drugs, pesticides and metabolites in forensic post-mortem blood samples.

Forensic post-mortem toxicological data provide valuable information for the elucidation of cause of death. However, this is still not routine practice in Brazilian laboratories. This study investigated the presence of illicit and prescription drugs, pesticides and metabolites in 111 post-mortem blood samples from cases investigated by the Forensic Medical Institute of the Federal District, Brazil. Quantitative analysis was performed for 14 analytes using a validated programmed temperature vaporisation-large volume injection-gas chromatography-mass spectrometry method, which was also used as screening (qualitative analysis) for an additional 19 substances of forensic interest. At least one analyte was found in 61.2% of the samples, of which 34 were related to homicide, 15 to accidental death and 10 to suicide cases. The victims were 14-72 years old. The benzodiazepines diazepam, midazolam and 7-aminoflunitrazepan were detected in 46% of the positive samples (0.02-1.12 µg/mL; midazolam only qualitative). Cocaine was found in 34% (0.02-4.07 µg/mL), associated with substances commonly used as cocaine adulterants (e.g. caffeine, lidocaine and phenacetin). Three suicide cases involved the illegal rodenticide chumbinho, residues of which were found in the gastric content, and blood samples showed the presence of terbufos (0.03 and 0.04 µg/mL) and carbofuran (27.3 µg/mL). These results are discussed, along with autopsy and crime-scene information.

Mass spectrometric approaches in impaired driving toxicology.

Driving under the influence of prescribed or illegal drugs increases the risk of having road accidents, just like driving under the influence of alcohol. In forensic toxicology, an increasing number of blood samples must be analyzed for drugs. Immunoassays tailored for a limited number of drugs (of abuse) are usually applied as prescreening tests at the roadside and/or in the laboratory. However, many other common drugs, such as anesthetics, antidepressants, antiepileptics, antihistamines, newer designer drugs, herbal drugs, neuroleptics (antipsychotics), opioids, or sedative-hypnotics, can also impair drivers. Therefore, this paper reviews multianalyte single-stage and tandem gas or liquid chromatography-mass spectrometry (GC-MS or LC-MS) procedures for the screening, identification, and validated quantification of such drugs in blood that have been reported since 2003. Basic information about the biosample assayed, workup, chromatography, the mass spectral detection mode, and validation data is summarized in tables. The pros and cons of the reviewed procedures are critically discussed, particularly with respect to their probable usefulness in impaired driving toxicology.

Risk of drug-induced photosensitivity: focus on spectroscopic and molecular characteristics.

BACKGROUND: Drug-induced photosensitivity is difficult to predict and remains a challenge for both the dermatological clinical practice and pharmacovigilance. PURPOSE: To assess the association between spectroscopic and molecular characteristics and the occurrence of photosensitivity reactions. METHODS: For 143 well-known photosensitisers (e.g. tetracyclines, diuretics), we retrieved information on spectroscopic and molecular parameters, including: absorption maximum lambda(max), molar absorption coefficient epsilon, area under the absorption curve (AUC), molecular weight and configuration, hetero and aromatic halogen atoms, lipophilicity (log P) and acid/base status (pKa). In the WHO-ADR database, all reports with suspected adverse drug reactions of the study drugs were selected. We identified all reports on photosensitivity reactions and defined them as cases. All other reports were selected as non-cases. A case-non-case approach was performed to assess the spectroscopic and molecular exposure variables as a factor for photosensitivity reactions. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: A lambda(max) between 290 and 320 nm (OR 3.74, 95% CI 3.45-4.06), and an epsilon > 20,000 M(-1) cm(-1) (OR 5.49, 95% CI 5.10-5.92) were highly associated with the reporting of photosensitivity reactions. Risk of the photosensitivity reactions was significantly increased among intermediate or high AUCs compared to low AUC. Low molecular weight and aromatic halogen atoms were associated with photosensitivity reactions (OR 2.37, 95% CI 2.07-2.71 resp. OR 3.37, 95% CI 3.15-3.61) as were log p < 1 and pKa < 7. CONCLUSION: The reporting of photosensitivity reactions to established phototoxic drug classes is strongly influenced by spectroscopic and physicochemical characteristics of individual drugs.

[Local straight line screening method for the detection of Chinese proprietary medicines containing undeclared prescription drugs].

The present paper constructs a new approach named local straight-line screening (LSLS) to detect Chinese proprietary medicines (CPM) containing undeclared prescription drugs (UPD). Different from traditional methods used in analysis of multi-component spectrum, LSLS is proposed according to the characteristics of original infrared spectra of the UPD and suspected CPM, without any pattern recognition or concentration model establishment. Spectrum-subtraction leads to the variance in local straight line, which serves as a key in discrimination of whether suspected CPD is adulterated or not. Sibutramine hydrochloride, fenfluramine hydrochloride, sildenafil citrate and lovastatin were used as reference substances of UPD to analyze 16 suspected CPM samples. The results show that LSLS can obtain an accurate quantitative and qualitative analysis of suspected CPM. It is possible for the method to be potentially used in the preliminary screening of CPM containing possible UPD.

Evaluation of compounded aqueous milbemycin oxime: issues with formulation potency and reproducibility.

OBJECTIVES: To determine the potency and reproducibility of milbemycin oxime when compounded as an aqueous suspension (20 mg/mL). MATERIALS AND METHODS: Preparation choice reflected current prescribing practices. Samples were acquired by prescription from two national veterinary compounding pharmacies at three time points. Two different storage conditions were evaluated and sampled at four time points from the order date (day 7, 14, 21 and 28). Milbemycin oxime recovery was performed by solid-phase extraction and concentration strength measured via high-performance liquid chromatography. RESULTS: The average concentration on day 7 for Pharmacy A samples was 16.29 mg/mL [confidence interval (CI): 15.66 to 16.92] with a coefficient of variation (CV) = 11%, while for Pharmacy B it was 20.46 mg/mL (CI: 19.83 to 21.08) with CV = 22%. The mean decrease in concentration over 28 days for Pharmacy A was 22% (CI: 9% to 34%) while Pharmacy B was 18% (CI: 2% to 35%). CLINICAL SIGNIFICANCE: The compounded milbemycin oxime suspensions evaluated in this study deviated by more than 10% from their labelled strength in five of the six lots. Clinical efficacy of compounded milbemycin oxime suspensions remains unknown and the use of these products should be discouraged at this time.

A Rapid Dilute-and-Shoot UPLC-MS/MS Assay to Simultaneously Measure 37 Drugs and Related Metabolites in Human Urine for Use in Clinical Pain Management.

BACKGROUND: Monitoring of medication compliance and drug abuse is used by clinicians to increase patient prescription drug compliance and reduce illicit drug abuse and diversion. Despite available immunoassays, chromatography-mass spectrometry-based methods are considered the gold standard for urine drug monitoring owing to higher sensitivities and specificities. Herein, we report a fast, convenient ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay to detect or quantify 37 clinically relevant prescription drugs, drugs of abuse, and related glucuronides and other metabolites in human urine by single diluted sample injection. METHODS: Analytes consisted of prescription and illicit opioids, benzodiazepines, and drugs of abuse, including parent compounds and glucuronidated and nonglucuronidated metabolites. Urine samples were diluted with water and supplemented with deuterated internal standards without enzymatic hydrolysis, analyte extraction, or sample purification. Analytes were separated by reversed-phase UPLC and quantified by positive-mode electrospray ionization and collision-induced dissociation MS. Assay validation followed Food and Drug Administration bioanalytical guidelines. RESULTS: Total analytical run time was 5.5 min. All analytes demonstrated acceptable inter- and intraassay accuracy, imprecision, and linearity throughout clinically relevant analytical ranges (1-2000 ng/mL, depending on analyte). All analytes demonstrated acceptable selectivity, stability, matrix effects, carryover, and performance compared to national reference laboratory or previously validated in-house methods. A total of 23 and 14 analytes were validated for quantitative and qualitative testing, respectively. CONCLUSIONS: A convenient UPLC-MS/MS assay for simultaneously monitoring 37 analytes in human urine was validated for use in pain management testing. Advantages of this multiplex assay include facile sample preparation and higher-throughput definitive detection including glucuronide metabolite quantification.

Express detection of expired drugs based on near-infrared spectroscopy and chemometrics: A feasibility study.

Levofloxacin is a third-generation fluoroquinolone antimicrobials drug that inhibits bacterial DNA replication. Driven by huge profit, one kind of particular counterfeit, e.g., repackaged expired tablets, becomes very common especially in developing countries. The feasibility of identifying expired levofloxacin tablets by combining NIR spectroscopy with chemometrics was investigated. Five kinds of levofloxacin samples from different manufacturers were collected for experiment. Two types of expired mode were considered and a simple model-independent algorithm was used for feature selection. Principal component analysis (PCA) was used for exploratory analysis and simple discriminant analysis. Taking seventy samples as the target class, a final one-class model based on Data Driven Soft Independent Modeling by Class Analogy with abbreviation DD-SIMCA was constructed, which achieved 97% sensitivity and 100% specificity on the independent set composed of 34 unexpired and 128 expired tablets. These results confirm that the combination of NIR spectroscopy, feature selection and class-modeling is feasible for identifying the expired levofloxacin tablets. Such a method can be extended to the analysis of similar drugs.