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Chemical Communications (Cambridge,... May 2019We describe the synthesis of pharmaceutically relevant co-crystals by solvent-free sonochemistry starting from solid reagents. Employing a standard ultrasonic cleaning...
We describe the synthesis of pharmaceutically relevant co-crystals by solvent-free sonochemistry starting from solid reagents. Employing a standard ultrasonic cleaning bath, quantitative conversions occurred within 20-60 minutes to give co-crystals of paracetamol and aspirin with a range of co-formers. As well as the utility of the method, the work raises interesting mechanistic questions regarding acoustic cavitation with no liquid phase being present.
Topics: Acetaminophen; Crystallization; Pharmaceutical Preparations; Powder Diffraction; Solvents; Ultrasonic Waves
PubMed: 31011746
DOI: 10.1039/c9cc00013e -
International Journal of Pharmaceutics Aug 2004It is well known that the presence of impurities can dramatically affect the nucleation, morphology, and chemical properties of crystals. Although literature is replete...
It is well known that the presence of impurities can dramatically affect the nucleation, morphology, and chemical properties of crystals. Although literature is replete with examples of impurity or additive-induced modifications of crystals, few have examined the interaction of these compounds with distinct growing faces. In this study, we utilize atomic force microscopy (AFM) and scanning electron microscopy (SEM) to investigate the influence of two structurally related additives of paracetamol (acetaminophen) on its crystal morphology. We also probe, in situ, the effects of these additives on the morphology and growth rate of steps on the (0 0 1) face of the crystal. This study, in conjunction with further investigations, aims to establish the specific mechanisms of inhibition of these additives on each face of paracetamol, and provide a means of overcoming the poor compaction behaviour of paracetamol.
Topics: Acetaminophen; Crystallization; Drug Contamination
PubMed: 15265554
DOI: 10.1016/j.ijpharm.2004.05.010 -
Fresenius' Journal of Analytical... Jul 2000A solid-phase extraction method routinely used for serum samples was improved and applied to the qualitative and quantitative determination of paracetamol in different...
A solid-phase extraction method routinely used for serum samples was improved and applied to the qualitative and quantitative determination of paracetamol in different body fluids, e.g. blood, urine, cerebrospinal fluid, synovial fluid, vitreous humor, and in tissue samples. A very simple method showed best results: Body fluids were mixed with phenacetine as internal standard and phosphate buffer (pH 6.8). Then protein was precipitated using acetonitrile. After strong centrifugation the supematant was transferred to a preconditioned Bakerbond C18-SPE-column. Elution with methanol without a prior washing step showed best recovery rates. The extracts were investigated using high-performance liquid chromatography with ultraviolet detection, a photometrical and an immunochemical method.
Topics: Acetaminophen; Body Fluids; Brain Chemistry; Chromatography, High Pressure Liquid; Humans; Indicators and Reagents; Kidney; Liver; Poisoning; Spectrophotometry, Ultraviolet; Synovial Fluid; Vitreous Body
PubMed: 11225839
DOI: 10.1007/s002160000420 -
The American Journal of Pathology Feb 1991Acetaminophen overdose causes severe hepatotoxicity in humans and laboratory animals, presumably by metabolism to N-acetyl-p-benzoquinone imine: and binding to cysteine...
Acetaminophen overdose causes severe hepatotoxicity in humans and laboratory animals, presumably by metabolism to N-acetyl-p-benzoquinone imine: and binding to cysteine groups as 3-(cystein-S-yl)acetaminophen-protein adduct. Antiserum specific for the adduct was used immunohistochemically to demonstrate the formation, distribution, and concentration of this specific adduct in livers of treated mice and was correlated with cell injury as a function of dose and time. Within the liver lobule, immunohistochemically demonstrable adduct occurred in a temporally progressive, central-to-peripheral pattern. There was concordance between immunohistochemical staining and quantification of the adduct in hepatic 10,000g supernate, using a quantitative particle concentration fluorescence immunoassay. Findings include: 1) immunochemically detectable adduct before the appearance of centrilobular necrosis, 2) distinctive lobular zones of adduct localization with subsequent depletion during the progression of toxicity, 3) drug-protein binding in hepatocytes at subhepatotoxic doses and before depletion of total hepatic glutathione, 4) immunohistochemical evidence of drug binding in the nucleus, and 5) adduct in metabolically active and dividing hepatocytes and in macrophagelike cells in the regenerating liver.
Topics: Acetaminophen; Animals; Dose-Response Relationship, Drug; Immunohistochemistry; Liver; Male; Mice; Time Factors; Tissue Distribution
PubMed: 1992763
DOI: No ID Found -
Annals of Clinical Biochemistry May 2011Glucose-6-phosphate dehydrogenase (G6PD), an X-linked hereditary deficiency, is the most common of all clinically significant enzyme defects. While many drugs are...
Glucose-6-phosphate dehydrogenase (G6PD), an X-linked hereditary deficiency, is the most common of all clinically significant enzyme defects. While many drugs are responsible for haemolytic anaemia in G6PD-deficient patients, acetaminophen's imputability is still under debate, although an overdose of this drug can provoke acute haemolytic events. We report a case of a Philipino child carrying the G6PD-Vanua Lava mutation with acute haemolytic crisis related to infection in progress and acetaminophen's administration. Fever and concomitant infection, through an increment of erythrocyte glutathione depletion, sensitized the infant to the haemolytic event. In this condition, acetaminophen (or paracetamol [PCM]) was capable of inducing a haemolytic crisis in our G6PD-deficient patient although administered under standard conditions. PCM seems to have induced the haemolytic event, probably by the alteration of its catabolism due to dehydration and fever. The enzymatic G6PD instability associated to the presence of the G6PD-Vanua Lava mutation could have led to an increment of red blood cells' sensitivity to lysis; hence, it is possible that PCM toxicity may also be due to the presence of this particular mutation. Finally, we propose a new biochemical classification of this G6PD variant.
Topics: Acetaminophen; Child, Preschool; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Infections; Male; Mutation; Philippines
PubMed: 21441392
DOI: 10.1258/acb.2010.010163 -
Magnetic Resonance in Medicine Mar 19881H NMR spectra of urine and plasma from subjects who had taken paracetamol (acetaminophen) at a therapeutic dose or in self-poisoning episodes (both fatal and nonfatal)...
1H NMR spectra of urine and plasma from subjects who had taken paracetamol (acetaminophen) at a therapeutic dose or in self-poisoning episodes (both fatal and nonfatal) are compared. They provide convenient metabolic profiles. For overdose cases, intense resonances corresponding to high levels of both drug and endogenous metabolites are observed. The ratios of glucuronide to sulfate conjugates are unusually high in urine from overdose cases. Elevated levels of the cysteinyl and N-acetyl cysteinyl conjugates reflect increased glutathione conjugation in the liver. The observed excretion of high levels of amino acids by overdose subjects is suggestive of drug-induced hepatic damage. No resonances for drug metabolites are detected in plasma samples. However, characteristic and abnormally intense resonances for the amino acids Phe, Tyr, His, Gln, Pro, Ala, Val, Lys, Met, Ser, and Thr are indicative of severe liver failure and disruption of normal deamination and transamination processes.
Topics: Acetaminophen; Female; Humans; Magnetic Resonance Spectroscopy; Male; Suicide, Attempted
PubMed: 3362065
DOI: 10.1002/mrm.1910060308 -
British Medical Journal Jul 1976
Topics: Acetaminophen; Child, Preschool; Humans
PubMed: 974512
DOI: 10.1136/bmj.2.6029.235-c -
Nursing Times Jul 1977
Topics: Acetaminophen; Humans
PubMed: 887438
DOI: No ID Found -
Singapore Medical Journal Aug 1993
Topics: Acetaminophen; Acetylcysteine; Charcoal; Drug Overdose; Gastric Lavage; Humans; Liver
PubMed: 8266195
DOI: No ID Found -
Mutation Research 1988Acetaminophen (paracetamol) showed mutagenicity to Salmonella typhimurium TA100 and TA98 either with or without S9 mix when treated with excess nitrite in acidic...
Acetaminophen (paracetamol) showed mutagenicity to Salmonella typhimurium TA100 and TA98 either with or without S9 mix when treated with excess nitrite in acidic solution. The mutagen was isolated and identified as 4-acetylamino-6-diazo-2,4-cyclohexadienone. Mutation tests and product analysis by high-performance liquid chromatography, however, suggested that this type of mutagen was hardly formed in the digestive tract of normal subjects.
Topics: Acetaminophen; Chromatography, High Pressure Liquid; Mutagens; Nitrites; Salmonella typhimurium
PubMed: 3057376
DOI: 10.1016/0165-7992(88)90024-3