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PubMedDate not supplied

Pralidoxime and l-lactate effects in vitro on the inhibition of acetylcholinesterase by paraoxon: pralidoxime does not confer superior protection.

Intoxication with the organophosphorus compound paraoxon (POX), an inhibitor of serine hydrolases, is frequent. Although oximes are the only enzyme reactivators presently available, clinical experience with their use was rather disappointing. Recent work has shown that under certain conditions l-lactate is also able to reduce in vitro the POX inhibition of butyrylcholine- and acetylcholineesterase (BChE and AChE). To assess the practical relevance, if any, of these findings, the protective effects of pralidoxime (PRX) and those of lactate had to be compared in the same in vitro model. Effects of PRX on the inhibition of AChE by POX were assessed in vitro in plasma of 12 (six male and six female) healthy human volunteers. The determinations were repeated using different oxime and different POX concentrations. The AChE activity determinations were performed using the following sampler: sample BL-baseline (or untreated plasma); sample a-after addition of POX to plasma (pl + POX); sample b-after POX and plasma were incubated and then oxime was added (pl + POX/PRX); sample c-after addition of oxime to plasma (pl + PRX); sample d-after oxime and plasma were incubated and then POX was added (pl + PRX/POX); sample e-after oxime and POX were incubated and then added to plasma (PRX + POX/pl). Results were corrected for spurious enzyme 'pseudo-activity' due to interaction between PRX and substrate (acetylthiocholine) in the absence of enzyme. In the micro- and millimolar ranges, PRX is able to protect in vitro AChE from inhibition by POX when added to human plasma prior to POX or when incubated with POX prior to addition to plasma. Adding PRX to plasma after POX has no protective effect. The PRX results were compared statistically with historical lactate data (obtained under identical conditions) using the Wilcoxon matched pairs test, with significance assumed for p = 0.01. No difference between PRX and lactate's protective effect on the AChE inhibition by POX was found in the in vitro model used. We therefore conclude that in vivo testing of lactate as a POX protective agent is warranted.

Acetylcholinesterase↗
PubMed2005

Organic phosphorus compounds--nerve agents.

The organic phosphorous compounds (OPC) include both the military grade nerve agents and the organic phosphorous pesticides. The major mechanism of OPC toxicity is through inhibition of acetylcholinesterase in neuronal synapses leading to excess acetylcholine and overstimulation of target organs. Signs and symptoms depend on the affinity of the OPC for muscarinic versus nicotinic receptors, and are likely to include both. Muscarinic symptoms may include diarrhea, urination, bronchospasm, bronchorrhea, emesis, and salivation. Nicotinic symptoms such as paralysis and fasciculations may also occur. Central nervous system toxicity may include seizures, altered mental status, and apnea, and require prompt intervention. Treatment includes early airway and ventilatory support as well as antidotal therapy with atropine, pralidoxime, and diazepam. Goals of therapy include prevention and rapid treatment of hypoxia and seizures, as these are linked to patient outcome.

Antidotes↗
PubMed2005

[Determination of pralidoxime chloride in rat plasma by high performance liquid chromatography].

OBJECTIVE: To provide a reference for clinically curing organophosphrous compounds Poisoning. A high performance liquid chromatography method has been developed for determination of pralidoxime chloride in rat plasma. BECKMAN ODS C18 column, Waters Model 510 HPLC pump and 996 photodiode Detector were used. The mobile phase consisted of 7.5% acetonitrile and 92.5% (20nmol/L NaH2PO4, 0.2% C8H17SO3 Na, pH3.0, adjusted by H3PO4 Solution) the flow rate was 1.0mol/min. detection wavelength was set at 296. The samples were pretreated with acetonitrite. The results show a good liner correlation between pralidoxime chloride concentration(from 1.0 - 5.0 microg/ml) and absorption intensity. The detection limit is 0.5 microg/ml with signal to noise ratio of 2. The intra-assay and inter-assay coefficients of variation were 1.35% and 2.73%. The recoveries for plasma were in ranges of 76% - 84%.

Animals↗
PubMed2004

Organophosphate-induced convulsions and prevention of neuropathological damages.

Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.

Acetylcholinesterase↗
PubMedDate not supplied

Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study.

BACKGROUND: Although more than 100 organophosphorus insecticides exist, organophosphorus poisoning is usually regarded as a single entity, distinguished only by the compound's lethal dose in animals. We aimed to determine whether the three most common organophosphorus insecticides used for self-poisoning in Sri Lanka differ in the clinical features and severity of poisoning they cause. METHODS: We prospectively studied 802 patients with chlorpyrifos, dimethoate, or fenthion self-poisoning admitted to three hospitals. Blood cholinesterase activity and insecticide concentration were measured to determine the compound and the patients' response to insecticide and therapy. We recorded clinical outcomes for each patient. FINDINGS: Compared with chlorpyrifos (35 of 439, 8.0%), the proportion dying was significantly higher with dimethoate (61 of 264, 23.1%, odds ratio [OR] 3.5, 95% CI 2.2-5.4) or fenthion (16 of 99, 16.2%, OR 2.2, 1.2-4.2), as was the proportion requiring endotracheal intubation (66 of 439 for chlorpyrifos, 15.0%; 93 of 264 for dimethoate, 35.2%, OR 3.1, 2.1-4.4; 31 of 99 for fenthion, 31.3%, 2.6, 1.6-4.2). Dimethoate-poisoned patients died sooner than those ingesting other pesticides and often from hypotensive shock. Fenthion poisoning initially caused few symptoms but many patients subsequently required intubation. Acetylcholinesterase inhibited by fenthion or dimethoate responded poorly to pralidoxime treatment compared with chlorpyrifos-inhibited acetylcholinesterase. INTERPRETATION: Organophosphorus insecticide poisoning is not a single entity, with substantial variability in clinical course, response to oximes, and outcome. Animal toxicity does not predict human toxicity since, although chlorpyrifos is generally the most toxic in rats, it is least toxic in people. Each organophosphorus insecticide should be considered as an individual poison and, consequently, patients might benefit from management protocols developed for particular organophosphorus insecticides.

Acetylcholinesterase↗
PubMed1997

Importance of aspartate-70 in organophosphate inhibition, oxime re-activation and aging of human butyrylcholinesterase.

Asp-70 is the defining amino acid in the peripheral anionic site of human butyrylcholinesterase (BuChE), whereas acetylcholinesterase has several additional amino acids, the most important one being Trp-277 (Trp-279 in Torpedo AChE). We studied mutants D70G, D70K and A277W to evaluate the role of Asp-70 and Trp-277 in reactions with organophosphates. We found that Asp-70 was important for binding positively charged echothiophate, but not neutral paraoxon and iso-OMPA. Asp-70 was also important for binding of positively charged pralidoxime (2-PAM) and for activation of re-activation by excess 2-PAM. Excess 2-PAM had an effect similar to substrate activation, suggesting the binding of 2 mol of 2-PAM to wild-type but not to the D70G mutant. A surprising result was that Asp-70 was important for irreversible aging, the D70G mutant having a 3- and 8-fold lower rate of aging for paraoxon-inhibited and di-isopropyl fluorophosphate-inhibited BuChE. Mutants of Asp-70 had the same rate constants for phosphorylation and re-activation by 2-PAM as wild-type. The A277W mutant behaved like wild-type in all assays. Our results predict that people with the atypical (D70G) variant of BuChE will be more sensitive to the toxic effects of echothiophate, but will be equally sensitive to paraoxon and di-isopropyl fluorophosphate. People with the D70G mutation will be resistant to re-activation of their inhibited BuChE by 2-PAM, but this will be offset by the lower rate of irreversible aging of inhibited BuChE, allowing some regeneration by spontaneous hydrolysis.

Acetylcholinesterase↗
PubMed1990

Respiratory failure of acute organophosphate and carbamate poisoning.

Respiratory failure (RF) developed in 43 (40.2 percent) of 107 patients with acute organophosphate or carbamate poisoning; 22 (51.2 percent) died. The 64 patients who did not develop RF survived. All cases of RF developed within 96 hours after poisoning: within 24 hours in 35 patients (acute onset) and between 24 and 96 hours in eight patients (subacute onset). Severity of poisoning was the primary determinating factor for RF. Cardiovascular collapse and pneumonia were also associated with RF. In 19 patients with cardiovascular collapse, 17 had acute onset of RF and two had subacute onset. In 28 patients with pneumonia, 17 developed acute onset of RF and eight developed subacute onset. No organophosphorus compound caused RF more frequently than another. The duration of ventilator support for subacute RF was significantly longer than for acute RF (287 +/- 186 vs 115 +/- 103 hours, p = 0.02). The use of pralidoxime did not reduce the incidence of RF. We found that severity of poisoning, cardiovascular collapse, and pneumonia were the predisposing factors to RF. The golden time for treatment of acute organophosphate or carbamate poisoning was the initial 96 hours. No RF occurred after this time. Aggressive treatment and prevention of the above three factors will reduce the incidence of RF, or in other words, reduce the mortality.

Acute Disease↗
PubMed1986

Management of acute childhood poisonings caused by selected insecticides and herbicides.

Most childhood exposures to insecticides and herbicides do not result in poisonings. Decontamination and observation are usually adequate treatments. The most frequent exposures involve carbamate and organophosphate insecticides. These compounds inhibit acetylcholinesterase, resulting in cholinergic signs that are reversible with atropine administration. Recent reports from poison control centers indicate that organophosphates have been associated with most of the serious childhood poisonings. Pralidoxime, a cholinesterase reactivator, must be administered along with atropine to patients with serious organophosphate poisoning, to reverse nicotinic receptor effects--in particular, respiratory paralysis. Although carbamates and organophosphates may cause clinically indistinguishable physical signs, pralidoxime therapy may be contraindicated for carbamate intoxications. In the event of a serious poisoning caused by a combination of organophosphate and carbamate insecticides, or by an unknown cholinergic agent, pralidoxime should not be withheld. Many organochlorine insecticides are restricted or are no longer available in the United States. CNS excitation and seizures, manifestations of organochlorine intoxication, can occur following ingestion or inappropriate application of the 1 per cent topical formulation of lindane used to treat scabies and lice. Treatment of such intoxication consists of decontamination measures and anticonvulsant administration. Pyrethrins are generally nontoxic in doses commonly ingested. Individuals with an allergic history may be at greatest risk for the most common adverse effects, contact dermatitis and hypersensitivity reactions. Of all insecticides or herbicides, paraquat is the most toxic. Any exposure to paraquat must be evaluated, even if several days have passed since the herbicide was ingested. Signs of pulmonary status deterioration usually portend a grave prognosis in paraquat poisoning. Despite in vitro toxicity similar to paraquat, diquat does not cause lung effects in human poisonings, and reported deaths have been from other causes. Poisoned patients who receive appropriate and timely treatment are virtually assured of complete recovery from most insecticide and herbicide poisonings. Deaths and long-term sequelae most often result from respiratory complications, which may occur as complications of the intoxication or from other constituents in the insecticide or herbicide formulation. Good supportive care with meticulous attention to, and anticipation of, respiratory complications is absolutely essential to prevent long-term sequelae or death from hypoxia.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗
PubMed1997

Pralidoxime continuous infusion in the treatment of organophosphate poisoning.

OBJECTIVE: To report a case of organophosphate poisoning treated with a continuous infusion of pralidoxime chloride. CASE SUMMARY: A 27-year-old white man presented with extreme agitation, muscle weakness and fasciculations, and respiratory failure after ingesting an organophosphate pesticide (Dursban, active ingredients chlorpyrifos and xylene) as a suicide attempt. Atropine sulfate and pralidoxime chloride were administered intermittently, but the patient continued to be extremely agitated and have muscle fasciculations. Subsequently, a continuous intravenous infusion of pralidoxime (8 mg/mL concentration) at 500 mg/h was initiated to help control breakthrough nicotinic symptoms. Therapy with atropine and pralidoxime was continued for approximately 72 hours. Therapy was discontinued due to the predominance of anticholinergic symptoms and the patient's increased awareness. DISCUSSION: Severe organophosphate poisoning with nicotinic and/or central manifestations should be treated with pralidoxime in addition to atropine. The rationale supporting the use of pralidoxime as a continuous infusion in this case includes: (1) slow absorption of organophosphate compounds following exposure to large quantities, (2) unknown quantity ingested, (3) delayed nicotinic effects from redistribution of lipid-soluble organophosphate and metabolic activation of phosphorothioates such as chlorpyrifos, and (4) intensive care monitoring. There is limited documentation in the literature of continuous infusions of pralidoxime used to treat organophosphate poisoning and the stability of the admixture is unknown. CONCLUSIONS: A continuous pralidoxime infusion successfully managed the prolonged nicotinic symptoms seen after ingestion of an organophosphate. A continuous infusion of pralidoxime may be particularly useful in cases of organophosphate poisoning when the extent of chemical exposure or quantity of chemical ingested is unknown but potentially toxic and the therapy must be symptomatically managed.

Adult↗
PubMed1980

Influence of various anions on intestinal disappearance of hexamethonium chloride and pralidoxime chloride in rats.

The intestinal transfer of two poorly absorbed quaternary ammonium drugs, hexamethonium chloride (I) and pralidoxime chloride (II), in the presence of various organic and inorganic anions was investigated in the rat using a modified in situ gut technique. The results were in agreement with those of the conventional in situ loop and plasms drug level techniques. Of the anions investigated, cholate, desoxycholate, taurocholate, phoscholate, dehydrocholate, and hyodesoxycholate had the greatest effect on increasing the amount and rate of disappearance of I. Similarly, the amount and rate of disappearance of II were enhanced markedly in the presence of phoscholate and trichloroacetate. The effect of cholate and phoscholate was investigated in detail. The membrane permeability and histological studies indicated that these anions may compromise the structural integrity of the membrane tissue, thus enhancing drug transfer.

Animals↗
PubMed1989

Ligand stabilization of cholinesterases.

Stabilization of fetal bovine serum (FBS) acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) (AChE) and human butyrylcholinesterase (acylcholine acylhydrolase, EC 3.1.1.8) (BuChE) by ligands and inhibitors was studied as a function of physical and chemical perturbation. Denaturation of AChE occurred as a binary exponential function in the temperature range studied (50-56 degrees C); the slower fraction progressively diminished as the temperature was increased. Inclusion of ligands or inhibitors stabilized AChE as a function of temperature, ligand concentration and time. The rank order in which ligands stabilized AChE was: edrophonium greater than decamethonium greater than pralidoxime chloride much greater than procainamide. BuChE denaturation was retarded by ligands in the order: decamethonium greater than procainamide greater than edrophonium greater than pralidoxime. A plot of the quotient of the fast/slow ratio against the log of the 50% inhibitory concentration (I50) for ligands providing substantial protection yielded a linear relation, suggesting that these compounds stabilized AChE by a common mechanism involving the anionic site of the active center. Urea-induced cholinesterase denaturation was also retarded by these ligands.

Acetylcholinesterase↗
PubMed1974

A central vasodepressor effect of Dyflos.

1 Cats were anaesthetized with pentobarbitone sodium and atropinized peripherally by intravenous injection of atropine methyl nitrate; the effect was examined of topical bilateral application of dyflos to the ventral surface of the medulla oblongata at a region lateral to the pyramids and caudal to the trapezoid bodies. Dyflos was applied by means of perspex rings; the volume of fluid placed in each ring was 10 mul.2 The topical application of dyflos (1-20 mg/ml) produced a fall in arterial blood pressure without changes in heart rate and, in experiments without artificial ventilation, tachypnoea with dissociation of thoracic and abdominal respiration.3 Atropine methyl nitrate (50 mg/ml) applied topically in the same way as dyflos, prevented or abolished its vasodepressor effect.4 The two reactivators of acetylcholinesterase, obidoxime (100-200 mg/ml) and pralidoxime mesylate (100-200 mg/ml), applied topically in the same way as dyflos, abolished its vasodepressor effect. The reactivator compound 30 (100 mg/ml), also a pyridinium aldoxime, did not have this effect.5 Obidoxime and pralidoxime mesylate also reversed the vasodepression produced by carbachol applied to the ventral surface of the brain stem but not the vasodepression produced by glycine similarly applied.6 The problem is discussed as to whether the reversal of the dyflos and carbachol-induced vasodepression by obidoxime and pralidoxime is due to acetylcholinesterase reactivation by dephosphorylation and decarbamylation respectively, to a central atropine-like action of these compounds or to a combination of both.

Acetylcholinesterase↗
PubMed1971

Cholinesterase inhibition by organophosphorus compounds and its clinical effects.

The clinical manifestations of acute poisoning by organophosphorus compounds in man are in accord with, initially, the stimulation and, later, the blocking of cholinergic transmission due to acetylcholinesterase inhibition. The manifestations involve mainly the para-sympathetic nerves, the neuromuscular junctions, and the central nerve synapses, and to a smaller degree the cholinergic sympathetic nerves. Miosis and muscle fasciculations are useful signs for diagnosis and for the control of therapy. Blood cholinesterase determination is the best diagnostic test. The cause of death is usually respiratory paralysis. Persistent manifestations have not been confirmed. Atropine and pralidoxime are effective for treatment and useful for diagnosis. Other oximes are promising but their clinical value has not been established. Poisoning by malathion is characterized by a prolonged course and by motor signs. Poisoning by organophosphorus compounds in man differs from animal experiments in several ways: in man, exposure may occur by several different routes, the manifestations are detected more easily, and therapy is given throughout the course of illness.

Acetylcholinesterase↗
PubMed2005

Protective drugs in acute large-dose exposure to organophosphates: a comparison of metoclopramide and tiapride with pralidoxime in rats.

Weak and reversible inhibitors of cholinesterase(s), when coadministered in excess with a more potent inhibitor such as organophosphates, can act in a protective manner. The benzamide compound, metoclopramide, confers some protection (putatively via this mechanism) for cholinesterases against inhibition by paraoxon both in vitro and in vivo, after chronic small-dose exposure. Tiapride is a related benzamide. In this study, we compared the protection by metoclopramide and tiapride in rats acutely exposed to large doses of paraoxon with the therapeutic "gold standard," pralidoxime. Group 1 received 1 micromol paraoxon (approximately 75% lethal dose), Group 2 received 50 micromol metoclopramide, Group 3 received 50 micromol tiapride, Group 4 received 50 micromol pralidoxime, Group 5 received 1 micromol paraoxon + 50 micromol metoclopramide, Group 6 1 micromol paraoxon + 50 micromol tiapride, and Group 7 1 micromol paraoxon + 50 micromol pralidoxime. All substances were administered intraperitoneally. The animals were monitored for 48 h and mortality was recorded at 30 min, 1, 2, 3, 4, 24, and 48 h. Blood was taken for red blood cell acetylcholinesterase measurements at baseline, 30 min, 24, and 48 h. With the exception of Group 7, in which some late mortality was observed, mortality occurred mainly in the first 30 min after paraoxon administration with minimal changes occurring thereafter. Mortality at 30 min was 0% in the metoclopramide, tiapride, and pralidoxime groups and 73 +/- 20 (paraoxon), 65 +/- 15 (paraoxon + metoclopramide), 38 +/- 14 (paraoxon + tiapride), and 13 +/- 19 (paraoxon + pralidoxime). Mortality at 48 h was 75 +/- 18 (paraoxon), 67 +/- 17 (paraoxon + metoclopramide), 42 +/- 16 (paraoxon + tiapride), and 27 +/- 24 (paraoxon + pralidoxime). Metoclopramide does not significantly influence mortality after acute large-dose paraoxon exposure. Both tiapride and pralidoxime significantly decreased mortality in our model. The protection conferred by tiapride was significantly less than that conferred by pralidoxime at 30 min, but was not significantly different at 24 and 48 h.

Acetylcholinesterase↗
PubMed2005

Novel neuroprotective effects with O-benzyl derivative of pralidoxime in soman-intoxicated rodents.

Pharmacological properties of oxime reactivators, not related to its ability to regenerate or reactivate nerve agent-inhibited acetylcholinesterase located at nerve synapses, have been reported to be important in protecting against poisoning by the nerve agent soman. Such non-reactivation effects have thus far been associated only with bispyridinium oximes. This study investigated the possibility of creating similar non-reactivation therapeutic effects in the mono-pyridinium ring oxime, pralidoxime (2-PAM) through attachment of alkyl groups of increasing chain length to the oxime functional group. Of the 4 derivatives investigated, only the O-benzyl derivative displayed strong sedative effects in mice and mitigated the development of motor convulsions following soman challenge (1.8 x LD50, subcutaneous). Anticonvulsant effects of this compound were enhanced by co-administration of a non-anticonvulsant dose of atropine sulfate. Administration of equivalent amount of other O-derivatives of pralidoxime failed to elicit similar anticonvulsant actions. Electroencephalographic (EEG) and histopathological studies using the rat model, intoxicated with a lethal dose (1.6 x LD50, s.c.) of soman, confirmed O-benzyl derivative neuroprotective capabilities when used as a pretreatment drug. Microdialysis studies revealed that its neuroprotective effect is related to its ability to attenuate soman-induced increase in acetylcholine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Pralidoxime in the treatment of carbamate intoxication.

The use of oxime reactivators of inhibited cholinesterase enzymes in poisoning by carbamate compounds has received mixed reviews in the medical literature. Data are limited and inconsistent on the possible role oxime reactivators might have in carbamate intoxication. Based on existing experience, atropine remains the treatment of choice and pralidoxime (2-PAM) is not recommended except in cases where atropine has first been proven inadequate, in serious mixed poisonings with both carbamate and organophosphorus compounds, or in serious poisonings by unidentified cholinesterase inhibitors.

Atropine↗
PubMed1983

High-performance liquid chromatographic determination of pralidoxime chloride and its major decomposition products in injectable solutions.

A high-performance liquid chromatographic (HPLC) method for the simultaneous determination of pralidoxime chloride (I) and its major decomposition products in an injectable formulation is described. I and its decomposition products were detected and quantitated by their UV absorbances at 270 nm, after being separated from related compounds and formulation excipients on a reverse-phase C-18 column using a mobile phase consisting of 52% acetonitrile and 48% of an aqueous solution containing 0.005 M phosphoric acid and 0.001 M tetraethylammonium chloride. The major decomposition products of I in the injectable formulation were identified by their retention times and stop-flow spectroscopy as 2-carboxy-N-methylpyridinium chloride, N-methyl-2-pyridone, 2-carbamoyl-N-methylpyridinium chloride, 2-hydroxymethyl-N-methylpyridinium chloride, and 2-cyano-N-methylpyridinium chloride. A substance of unknown identity also was detected in degraded solutions of I. Stop-flow spectroscopy, employing the spectral discrimination technique, showed that the method is specific for I. Recovery of I from a spiked placebo formulation averaged 99.9%. The accuracy of the method was also demonstrated for the decomposition products over a range of concentrations representing 1-50% decomposition. Replicate determinations of I in degraded solutions gave coefficients of variation of 1.0 and 1.5%, while the precision of determining the decomposition products range from 1.3 to 6.5%. Regression lines with correlation coefficients greater than 0.9999 were obtained for I and its decomposition products, and solutions of these compounds were shown to be stable in the mobile phase for several days. Results for I by the HPLC and USP procedures are compared.

Chromatography, High Pressure Liquid↗