The site is secure. BZ are weakly acidic and are therefore excluded from OF, resulting in low OF concentrations [7]. Chze M, Muckensturm A, Hoizey G, Ppin G, Deveaux M. Forensic Sci Int. The period of detection for benzodiazepines varies greatly according to the specimen type utilized for testing and the patients dosing regimen. 12% 38% 41% 1% 8% Fig. Aegis Sciences Corporation Study Shows Widespread Distribution of Xylazine Read More. Immunoassay. Tell your doctor if you have ongoing anxiety, depression, problems with memory or thinking, trouble sleeping, ringing in your ears, a burning or prickly feeling, or a crawling sensation under your skin. An official website of the United States government. Forensic Sci Int. J Anal Toxicol. This test measures the amount of clonazepam in your blood. Seal Beach, CA: Biomedical Publications; 2017.2. It can cause side effects such as . Brand names: KlonoPIN, KlonoPIN Wafer High dosage and long-term use increase the risk and severity of dependence and withdrawal symptoms. 2019 Sep 5;2019:2035492. doi: 10.1155/2019/2035492. HHS Vulnerability Disclosure, Help 2010 Mar 20;196(1-3):14-7. doi: 10.1016/j.forsciint.2009.12.037. Curr Drug Metab. Clonazepam, like other benzodiazepines, while being a first-line treatment for acute seizures, is not suitable for the long-term treatment of seizures due to the development of tolerance to the anticonvulsant effects. The characterization of human urine for specimen validity determination in workplace drug testing: a review. Such aberrant behavior should be considered in the context of the entire patient presentation with a provider using his or her clinical judgment to assess this possibility. Diazepam in particular has been noted to be detected longer in the urine of obese patients.4 Period of detection studies in toxicology are often limited, and special populations of patients are often excluded. These data illustrate the limitations of using a 200 ng/ mL cutoff to monitor clonazepam compliance and suggest that a cutoff of 40 ng/mL or less is needed to reliably monitor use of this drug. Clipboard, Search History, and several other advanced features are temporarily unavailable. [136], It is marketed under the trade name Rivotril by Roche in Argentina, Australia, Austria, Bangladesh, Belgium, Brazil, Bulgaria, Canada, Colombia, Costa Rica, Croatia, the Czech Republic, Denmark, Estonia,[137] Germany, Hungary, Iceland, Ireland, Italy, China, Mexico, the Netherlands, Norway, Portugal, Peru, Pakistan, Romania, Serbia, South Africa, South Korea, Spain, Turkey, and the United States; Emcloz, Linotril, Lonazep and Clonotril in India and other parts of Europe; under the name Riklona in Indonesia and Malaysia; and under the trade name Klonopin by Roche in the United States. 2009;1(5):937-52.13. Urinary analyses of the metabolite 7-aminoclonazepam (7-AC) can be helpful in monitoring drug abuse and in the context of suspected drug-facilitated sexual assaults (DFSA). Overdose symptoms may include extreme drowsiness, confusion, muscle weakness, or coma. [89] Clonazepam is generally not recommended for use in elderly people for insomnia due to its high potency relative to other benzodiazepines. The .gov means its official. Clonazepam is a benzodiazepine (ben-zoe-dye-AZE-eh-peen). Dosage forms: oral tablet (0.5 mg; 1 mg; 2 mg), oral tablet, disintegrating (0.125 mg; 0.25 mg; 0.5 mg; 1 mg; 2 mg) Sadrabadi EA, Khosravi F, Benvidi A, Shiralizadeh Dezfuli A, Khashayar P, Khashayar P, Azimzadeh M. Biosensors (Basel). [9] In addition, clonazepam decreases the utilization of 5-HT (serotonin) by neurons[111][112] and has been shown to bind tightly to central-type benzodiazepine receptors. [9], The elderly are especially susceptible to increased risk of harm from motor impairments and drug accumulation side effects. 2023 Jan 23:1-13. doi: 10.1007/s40264-022-01269-x. Federal government websites often end in .gov or .mil. The challenges of LC-MS/MS analysis of opiates and opioids in urine. The following urine samples were collected from each volunteer: one before CLO administration, and 6 h, and 1, 3, 5, 8, 10, 14, 21 and 28 days after. Your family or caregivers should also watch for sudden changes in your behavior. Ther Drug Monit. Withdrawal seizures and psychosis can occur in severe cases of withdrawal, and anxiety and insomnia can occur in less severe cases of withdrawal. Clonazepam's mode of action is to decrease abnormal electrical energy in the brain. Do not drink alcohol. [97][99][100][101] In turn, Phenytoin may lower clonazepam plasma levels by increasing the speed of clonazepam clearance by approximately 50% and decreasing its half-life by 31%. But be sure your healthcare provider knows Kempf J, Wuske T, Schubert R, Weinmann W. Pre-analytical stability of selected benzodiazepines on a polymeric oral fluid sampling device. Tell your doctor right away if you have any sudden changes in mood or behavior, or thoughts about suicide. 2008;9(8):827-443. Clipboard, Search History, and several other advanced features are temporarily unavailable. 0000003515 00000 n In the case of improper storage, drug degradation contributing to unexpected negative results may be possible. MeSH Therefore many addiction clinics perform oral fluid (OF) testing, which unlike urine is not subject to adulteration, to monitor CLON compliance. Due to the risks of tolerance and withdrawal seizures, clonazepam is generally not recommended for the long-term management of epilepsies. Possible adverse effects of use of benzodiazepines such as clonazepam during pregnancy include: miscarriage, malformation, intrauterine growth retardation, functional deficits, carcinogenesis, and mutagenesis. Use all medications as directed by your doctor. This site needs JavaScript to work properly. [9] Peak blood concentrations of 6.513.5ng/mL were usually reached within 12 hours following a single 2mg oral dose of micronized clonazepam in healthy adults. confusion, paranoia, nightmares, hallucinations; Drowsiness or dizziness may last longer in older adults. The https:// ensures that you are connecting to the Illicit Exposure: Sources of illicit exposure may include use of another persons prescription drug, acquisition of counterfeit or other illicit drugs unknowingly laced with benzodiazepines, or exposure to illicitly manufactured benzodiazepines which may share metabolites with FDA-approved benzodiazepines.3. 7-aminoclonazepam is superior to clonazepam for detection of clonazepam use in oral fluid by LC-MS/MS This test measures the amount of clonazepam in your blood. WARNING This product is not for human or veterinary use. may not be accurate if the sample is not handled properly. Clonazepam, like other benzodiazepines, may impair a person's ability to drive or operate machinery. -7-Aminoclonazepam (metabolite of clonazepam)-Diazepam (separate prescribable drug and . Key words: Clonazepam, 7-aminoclonazepam, pain management, LC-MS/MS, immunoassay, patient compliance Providers should use their independent medical judgment based on the clinical needs of the patient when making determinations of who to test, what medications to test, testing frequency, and the type of testing to conduct. %%EOF Ask your doctor before using opioid medication, a sleeping pill, a muscle relaxer, or medicine for anxiety or seizures. 0000004622 00000 n 2004 Oct 29;145(2-3):123-30. doi: 10.1016/j.forsciint.2004.04.066. You may also have this test if you are having side effects from clonazepam. Procedural Administration: Abenzodiazepine may be administered as an anxiolytic or sedative prior to medical procedures. [6][132] These metabolites are excreted by the kidney. Pain Physician. These medications share common metabolites, and distinguishing which compound was ingested may be impossible.1,2 Note the analytes in red boxes below that are both metabolites and drugs available as a prescription. Clonazepam may harm an unborn baby, but having a seizure during pregnancy could harm both mother and baby. [Benzodiazepine (clonazepam, nitrazepam, diazepam)]. In some cases, as with fentanyl, drugs are included on this list because the assay is also used to detect the drug in pharmaceutical preparations. Before Standard curves for CLO (500-4000 pg x mL(-1)) and 7-ACLO (50-2000 pg x mL(-1)) were prepared by spiking aliquots of negative urine. Using molecular similarity to highlight the challenges of routine immunoassay-based drug of abuse/toxicology screening in emergency medicine. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances. The degree of tolerance is more pronounced with clonazepam than with chlordiazepoxide. Drug class: benzodiazepine anticonvulsants. [24], Abrupt or over-rapid withdrawal from clonazepam may result in the development of the benzodiazepine withdrawal syndrome, causing psychosis characterised by dysphoric manifestations, irritability, aggressiveness, anxiety, and hallucinations. 65044. The mechanism of tolerance includes receptor desensitization, down regulation, receptor decoupling, and alterations in subunit composition and in gene transcription coding. Unable to load your collection due to an error, Unable to load your delegates due to an error. Abuse may lead to limited physical or psychological dependence. Urine drug testing in clinical practice: the art and science of patient care. Alcohol alone was responsible for over twice as many ED visits as clonazepam in the same study. Read the medication guide or patient instructions provided with each medication. Class/Isotype: IgG: Cross Reactivity: 7-aminoclonazepam, 7-aminoflunitrazepam, Delorazepam >10%; N-Desalkylflurazepam, Flunitrazepam >1%; Nitrazepam, Desmethyldiazepam, Diazepam : 1% Supplied In: . Drug monitoring of benzodiazepines is often performed in toxicology and pain management settings. Coloring the toilet water blue prior to sample collection and assessing the urine temperature within 4 minutes of collection (should be between 90F and 100F) are additional measures to check for sample tampering.5-6. In most cases, other drugs were also present. 0000011260 00000 n It is thought that benzodiazepines work by enhancing the activity of certain neurotransmitters in the brain. Contact the laboratory with any questions about the cross-reactivity of any specific drug with this assay. MISUSE CAN CAUSE ADDICTION, OVERDOSE, OR DEATH. Point of Care Testing ConsiderationsSome point-of-care testing (POCT) devices may result in a false positive for benzodiazepines in patients who are taking certain medications.6,11-17 Cross reactivity can occur with this type of testing among drugs with similar chemical structures.11 Non-benzodiazepine prescription, illicit, or over-the-counter drugs would not cause a false positive for benzodiazepines or benzodiazepine metabolites on Aegis definitive testing. Urine samples with such a low creatinine level are less concentrated, and urine drug concentrations may fall below the reporting threshold in such samples. 1988;10(1):21-6.9. Clonazepam is available as tablets and orally disintegrating tablets (wafers) an oral solution (drops), and as a solution for injection or intravenous infusion. Providers may consider the possibility of reduced absorption of drug and potential impact on unexpected negative results in these patients. We investigated the effects of ACZP on the GABA(A) receptor-mediated currents (I(GABA)) in neurons from the nucleus reticularis thalami (NRT) of the . This has been conjectured as a mechanism for high-dose effects on seizures in the study. Test results may vary depending on your age, gender, health history, and other things. Stay alert to changes in your mood or symptoms. In many cases, the result interpretation may be clarified by correctly indicating the patients prescribed medications when ordering testing. xb```b`` " ,@QU@CM^R2x_c Clipboard, Search History, and several other advanced features are temporarily unavailable. Would you like email updates of new search results? 1B Types of Drugs Detected NPS TID Prescription . Methods Find Exp Clin Pharmacol. Anti-epileptic drugs, benzodiazepines such as clonazepam in particular, should be reduced in dose slowly and gradually when discontinuing the drug to mitigate withdrawal effects. Benzodiazepines do not replace GABA, but instead enhance the effect of GABA at the GABAA receptor by increasing the opening frequency of chloride ion channels, which leads to an increase in GABA's inhibitory effects and resultant central nervous system depression. Clonazepam is used to treat certain seizure disorders (including absence seizures or Lennox-Gastaut syndrome) in adults and children. Your healthcare provider may also order other tests, including: 7-aminoclonazepam. The range of concentrations detected was from 73.0 pg x mL(-1) to 183.2 ng x mL(-1). 2000 Oct;24(7):614-20. doi: 10.1093/jat/24.7.614. Medically reviewed by Kaci Durbin, MD. In many cases, non-pharmacological treatments, such as relaxation therapy, psychotherapy, and avoidance of caffeine, can be an effective and safer alternative to the use of benzodiazepines for anxiety in pregnant women. [126] It has an elimination half-life of 1960 hours. Coronavirus (COVID-19): Latest Updates | Visitation PoliciesVisitation PoliciesVisitation PoliciesVisitation PoliciesVisitation Policies | COVID-19 Testing | Vaccine InformationVaccine InformationVaccine Information. As a result, drugs present at therapeutic concentrations may not always be detected. J Clin Pharmacol. This class of drug is also subject to misuse and is frequently included in urine drugs of abuse testing panels. Nihon Rinsho. FOIA Store at room temperature away from moisture, heat, and light. 0000005469 00000 n Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. Unable to load your collection due to an error, Unable to load your delegates due to an error. This is a substance your body makes from clonazepam. Continue reading. These stability issues along with as-needed dosing and/or low doses may further increase the likelihood of unexpected negative results. Detection Times of Diazepam, Clonazepam, and Alprazolam in Oral Fluid Collected From Patients Admitted to Detoxification, After High and Repeated Drug Intake. J Anal Toxicol. Clonazepam pregnancy and breastfeeding warnings. LC-MS/MS extends the range of drug analysis in pain patients. If the medication was directly administered to the patient by the treating provider, record of this may not be part of the patients PDMP report. [104], The safety profile of clonazepam during pregnancy is less clear than that of other benzodiazepines, and if benzodiazepines are indicated during pregnancy, chlordiazepoxide and diazepam may be a safer choice. Clonazepam's mode of action is to decrease abnormal electrical energy in the brain. The .gov means its official. Please enable it to take advantage of the complete set of features! [106] It acts by binding to the benzodiazepine site of the GABA receptors, which enhances the electric effect of GABA binding on neurons, resulting in an increased influx of chloride ions into the neurons. [80] Many studies have found that tolerance develops to the anticonvulsant properties of clonazepam with chronic use, which limits its long-term effectiveness as an anticonvulsant. During the validation of a laboratory-developed multiplex UPLC-MS/MS assay for quantifying benzodiazepines in human urine, we observed notable instability (greater than 20% nominal) in 7-aminoclonazepam (7AC) during prolonged freezing conditions by performing method comparisons and a conventional . It is not a diagnostic device. Detection of Nitrobenzodiazepines and Their 7-Amino Metabolites in Oral Fluid. Intentional dilution may occur either with intentional ingestion of copious amounts of water or by adding water to the urine sample from the restroom sink or toilet. World Psychiatry. A considerable amount of 7-aminoclonazepam (ACZP), a major metabolite of clonazepam (CZP), is present in the brain during CZP treatment, yet the pharmacological properties of ACZP remain unknown. Follow the directions on your prescription label and read all medication guides. 2013:416:80-58. Brahm NC, Yeager LL, Fox MD, Farmer KC, Palmer TA. Disclaimer. Clin Chim Acta. Losses of 7-aminoclonazepam in urine averaging 43% have been reported under refrigerated conditions at 2 months.7 A 76% drop in clonazepam concentration has occurred in an oral fluid specimen stored at room temperature overnight.8 Complete loss of clonazepam in oral fluid has occurred in 7 days at room temperature.9 In oral fluid, losses of 7-aminoclonazepam up to 20% and 33% have been observed at room and refrigerated temperatures, respectively, over a week.10 Providers may consider these known issues particularly when evaluating unexpected negative clonazepam results. [90], Clonazepam is not recommended for use in those under 18. The concentrations were thus similar among the groups, although the median value was highest in the postmortem group. Common clonazepam side effects may include: After you stop using clonazepam, get medical help right away if you have symptoms such as: unusual muscle movements, being more active or talkative, sudden and severe changes in mood or behavior, confusion, hallucinations, seizures, suicidal thoughts or actions. Your doctor will need to check your progress on a regular basis. PMC Clonazepam in particular is more prone to stability issues. If you use clonazepam during pregnancy, your baby could be born with life-threatening withdrawal symptoms, and may need medical treatment for several weeks. MeSH 8600 Rockville Pike Because of the complexity of this test, and because the test is not run in a quantitative mode, these sensitivities should only be used in concert with other clinical and historical data to guide clinical interpretation. treatment. We determined the optimal technical and clinical approach for the detection of CLON use using OF. Clonazepam, marketed as Klonopin and Rivotril, is a long-acting benzodiazepine with anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties. Benzodiazepine metabolism: an analytical perspective. In: Levine B, ed. 2013 Feb 23;74:213-22. doi: 10.1016/j.jpba.2012.11.002. 2007 Mar 2;166(2-3):209-17. doi: 10.1016/j.forsciint.2006.05.040. Efavirenz treatment and false-positive results in benzodiazepine screening tests. Patients dependent on clonazepam should be slowly titrated off under the supervision of a qualified healthcare professional to reduce the intensity of withdrawal or rebound symptoms. As a major metabolite, 7-aminoclonazepam may be used to monitor use of the parent drug, clonazepam. Storhaug LW, Enger A, Hjelmeland K, iestad EL, Vindenes V. Forensic Sci Int. J Anal Toxicol. Your test results may be different depending on the lab used. Doses for the elderly are recommended to be about half of that given to younger adults and are to be administered for no longer than two weeks. Acetaminophen (Tylenol) is a non-narcotic analgesic with antipyretic . The screening immunoassays cutoffs given are the concentrations above which the assay is reported as positive; note that a drug present below the cutoff will be reported as negative on an immunoassay screen even though it is present. J Anal Toxicol. 7-Aminoclonazepam. 0000001741 00000 n Using LC-MS/MS, clonazepam was detected in 297 traffic cases, 92 criminal cases (perpetrators or victims of a crime) and in 140 postmortem cases. Clonazepam can slow or stop your breathing, especially if you have recently used an opioid medication, alcohol, or other drugs that can slow your breathing. Drugs of abuse in oral fluid collected by two different sample kitsstability testing and validation sing ultra performance tandem mass spectrometry. Ask your doctor or pharmacist if you do not understand these instructions. It can cause side effects such as drowsiness . [23], It is also approved for treatment of typical and atypical absences (seizures), infantile myoclonic, myoclonic, and akinetic seizures. [125], It is effective for 68 hours in children, and 612 in adults. Unexpected benzodiazepine results may be indicative of noncompliance, drug misuse, or diversion, and we welcome your calls and e-mails for assistance in interpreting these results. Call your doctor if this medicine seems to stop working as well in treating your seizures or panic attacks. 215 0 obj <> endobj 2002 Oct;26(7):471-8. doi: 10.1093/jat/26.7.471. [113] Because clonazepam is effective in low milligram doses (0.5mg clonazepam = 10mg diazepam),[114][115] it is said to be among the class of "highly potent" benzodiazepines. This limits the utility of the comprehensive drug screen for monitoring compliance or for confirming the results of screening immunoassays. m@6lm -"`uX. It is extensively metabolised into pharmacologically inactive metabolites, with only 2% of the unchanged drug excreted in the urine. CLO was not detected in any of the samples. stinging sensation or pain. A highly sensitive NCI-GC-MS method for the simultaneous quantitation of CLO and its major metabolite 7-ACLO in urine was developed and validated. The stability of benzodiazepines in saliva. Providers may also consider recent GI illness in the interpretation of unexpected negative results. Disclaimer. National Library of Medicine government site. Accessibility Clonazepam is detected as the metabolite 7-aminoclonazepam. In settings of abuse or detoxification, the period of detection may be longer. Bioanalysis. You should be aware if anyone is using it improperly or without a prescription. Plasma levels of clonazepam can vary as much as tenfold between different patients. 2011;3367-77.11. As a class of drugs, benzodiazepines are among the drugs most commonly prescribed in the western hemisphere because of their efficacy, safety, low addiction potential, minimal side effects, and high public demand for sedative and anxiolytic agents. Epub 2012 Jul 19. [122] Benzodiazepines act via micromolar benzodiazepine binding sites as Ca2+ channel blockers and significantly inhibit depolarization-sensitive calcium uptake in experimentation on rat brain cell components. When was the patients last dose? Alprazolam (Xanax): Metabolizes to alpha-hydroxyalprazolam; reported as Alprazolam Clonazepam (Klonopin): Metabolizes to 7-aminoclonazepam; reported as Clonazepam Flurazepam: Metabolizes to 2-hydroxyethylflurazepam; reported as Flurazepam Lorazepam (Ativan): Metabolizes to lorazepam glucuronide; reported as Lorazepam Do not change your doses or medication schedule without your doctor's advice. You may have this test if it's possible you have taken an overdose of clonazepam. 0000009460 00000 n Remove an orally disintegrating tablet from the package only when you are ready to take the medicine. Keep the medication in a place where others cannot get to it. When the needle pricks your arm, you may feel a slight Application to forensic cases of drug facilitated crimes. Washington, D.C. AACC Press;2013:149-69.15. Stability of pain-related medications, metabolites, and illicit substances in urine. Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use clonazepam only for the indication prescribed. [10] Clonazepam binds to GABAA receptors, thus increasing the effect of the chief inhibitory neurotransmitter -aminobutyric acid (GABA). Clonazepam is a benzodiazepine prescription drug and is classified by the DEA as Schedule IV controlled substance under the federal Controlled Substances Act. [10][11] If used during pregnancy it may result in harm to the fetus. [12][13] It is available as a generic medication. Azole antifungals, such as ketoconazole, may inhibit the metabolism of clonazepam. [62] Carbamazepine has been tested in the treatment of clonazepam withdrawal but was found to be ineffective in preventing clonazepam withdrawal-induced status epilepticus from occurring. Version 2.73 51776-37-Aminoclonazepam [Mass/volume] in Urine by Confirmatory methodActive Part Description LP28541-8 7-Aminoclonazepam 7-Aminoclonazepam is a metabolite of clonazepam, a benzdiazepine drug used to treat or control seizures, panic attacks, and akathisia. Mandrioli R, Mercolini L, Raggi MA. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). 1983;23:369-765. ETHANOL <10 mg/dL ethanol reported as negative, Last updated 2023-02-02T16:38:32.834115+00:00, Contact: commserv@uw.edu | This site needs JavaScript to work properly. and transmitted securely. Test Result Name. Eur J Drug Metab Pharmacokinet. suicidal thoughts, and drowsiness. 0 eCollection 2019. 2004 Dec;62 Suppl 12:360-3. Gourlay DL, Heit HA, Caplan YH. Only two studies have reported detection times of 7-AC in urine after a single dose of clonazepam, and no previous studies have reported detection times after repeated . It can cause side effects such as drowsiness, problems with coordination, and . In addition, it is frequently used to treat drug addicts and is itself a popular drug of abuse. 215 23 Negrusz A, Moore CM, Kern JL, Janicak PG, Strong MJ, Levy NA. Clonazepam was the second most frequently implicated benzodiazepine in ED visits. [89][91], Doses higher than 0.51mg per day are associated with significant sedation. The test can also be used to monitor the level of clonazepam in your system throughout Intermolecular Interactions between Eosin Y and Caffeine Using. Deposition of 7-aminoclonazepam and clonazepam in hair following a single dose of Klonopin. Further information regarding specimen stability is available in the Aegis Clinical Reference Guide at https://www.aegislabs.com/resources/clinical-reference-guide/. 7AC should be the analyte measured in OF for the detection of CLON use. Bethesda, MD 20894, Web Policies arm. Stopping suddenly may cause increased seizures or unpleasant withdrawal symptoms. is a metabolite of the drug clonazepam (Klonopin) a central nervous system depressant of the benzodiazepine class. In blood, especially, the period of detection is generally limited to very recent use. Seizures are often treated with a combination of drugs. Baselt, RC. False negative immunoassay results may also occur due to failure of the assay to react to drug-specific markers such as alpha-OH-alprazolam, 7-aminoclonazepam, 2-hydroxyethylflurazepam, and lorazepam glucuronide.6,11,12,16,18-21. [10] Effects begin within one hour and last between six and twelve hours. Read and carefully follow any Instructions for Use provided with your medicine. Six of the volunteers had urine concentrations of 7-ACLO that peaked at 1 day after administration. [74], Like all benzodiazepines, clonazepam is a GABA-positive allosteric modulator. Other drugs may interact with clonazepam, including prescription and over-the-counter medicines, vitamins, and herbal products. 7-Aminoclonazepam; Addiction management; Clonazepam; Compliance; Oral fluid. Nordal K, iestad EL, Enger A, Christophersen AS, Vindenes V. Ther Drug Monit. Your doctor may occasionally change your dose. Epub 2006 Jun 30. Careers. medicines that don't need a prescription and any illegal drugs you may use. [citation needed] Clonazepam is also effective in the management of acute mania.

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