Methyl lidocaine

Nelson SD, Breck GD, Trager WF. In vivo metabolite condensations. Formation of Nl-ethyl-2-methyl-N3-(2,6-dimethylphenyl)-4-imidazolidinone from the reaction of a metabolite of alcohol with a metabolite of lidocaine. J Med Chem 1973 16(10) 1106-1112. 

Other API amide hydrolysis examples include chloramphenicol (12), indomethacin under alkaline conditions (13), lidocaine (14), azintamide (15), terazosin (16), flutamide (17), oxazepam, and chlordiazepoxide (18). Lidocaine does not readily hydrolyze in aqueous solution under thermal or basic conditions (Fig. 7) (19). The enhanced stability is due to the steric hindrance of the two o-methyl groups. Hydrolysis does occur more readily in acidic conditions rather than basic conditions presumably because the rate-limiting step, protonation of the carbonyl, is not affected by the steric hindrance of the o-methyl. 

Bicchi and Bertolino [193] analyzed a variety of pharmaceuticals for residual solvents. Samples were equilibrated directly or dissolved in a suitable solvent with a boiling point higher than that of the residual solvent to be determined. Equilibration conditions were 90 or 100°C for 20 min. A Perkin-Elmer HS-6 headspace sampler was used. The chromatographic phase chosen was a 6 x Vs in. column packed with Carbopack coated with 0.1% SP 1000. Residual ethanol in phenobarbital sodium was determined by a direct desorption method. An internal standard, /-butanol, was used. Typically, 0.44% of ethanol was detected (compared to a detection limit of 0.02 ppm). The standard deviation of six determinations was 0.026. Pharmaceutical preparations which were analyzed by the solution method included lidocaine hydrochloride, calcium pantothenate, methyl nicotinate, sodium ascorbate, nicotinamide, and phenylbutazone. Acetone, ethanol, and isopropanol were determined with typical concentrations ranging from 14 ppm for ethanol to 0.27% for acetone. Detection limits were as low as 0.03 ppm (methanol in methyl nicotinate). 

The selectivity of amperometric detection has been useful in simplifying the sample pretreatment steps in the determination of a number of drug products [82-86]. A method requiring no sample preparation using an amperometric detector and UV detector in series was developed for lido-caine hydrochloride injectable solutions [87]. The drug epinephrine is quantified with the amperometric detector, whereas lidocaine and methyl para-ben are detected by ultraviolet light. Disodium EDTA had to be added to the mobile phase to eliminate a peak response from iron leached from the stainless steel. 

There are two principle problems. The first is lack of resolution, for example, in the methanol/ammonia system, cocaine/procaine and ecgo-nine methyl ester/lidocaine are not well resolved and yet may occur together in the mixture. A further difficulty is added by the lack of specificity of the visualization reagents. None of the reagents used here are specific to this group of compounds. 

Mexiletine Hydrochloride. Mcxiletinc hydrochloride. l-methyl-2-(2.6-xylyloxy)cthylamine hydrochloride (Mexi-til) (pK.., 8.4), is a class IB ontiarrhythniic agent that is cffec-tive when given either intravenously or orally. It re.sembles lidocaine in po.ssessing a xylyl moiety but otherwise is diTfer-ent chemically. Mexiletine hydrochloride is an ether and is not subject to the hydrolysis common to the amides lidocaine and tocainide. Its mean half-life on oral administration is approximately 10 hours. 

A recent study has employed deuterium labeling to show that the mechanism for the oxidative N-demethylation of nicotine may involve two modes of breakdown for a proposed carbinolamine intermediate, dealkylation with formaldehyde formation and dehydration to an iminium ion.72 The formation of such an sp2-hybrid intermediate may help to explain why both a primary and substantial / -secondary deuterium isotope effect were observed for the N-deethylation of the antiarrhythmic agent, lidocaine.73 In contrast, only a primary isotope effect was observed on the rate of oxidative O-deethylation of deuterated analogs of the analgesic, phenacetin. 77 These results indicate differences in the mechanism of oxidative 0- and N-dealkylation. A final example of the use of secondary deuterium isotope effects in studying enzymes involved in drug metabolism revealed an SN-2-like transition state for the transfer of a methyl group catalyzed by catechol-O-methyl transferase.73... 

EMLA - local anaesthetic combination of lidocaine and prilocaine Entacapone - catechol-o-methyl transferase inhibitor Parkinson s disease Enoxaparin - low molecular weight heparin thrombosis prophylaxis prior to surgery Epoetin - erythropoietin replacement anaemia Erythromycin - antibiotic... 

Prilocaine (No. 10) represents an interesting situation in that the presence of only one o-methyl group has two consequences. A predictably shorter duration of action because of more facile amide hydrolysis, as compared with lidocaine, and a significant likelihood of methemoglobinemia at higher doses being produced by o-toluidine that results from this amide hydrolysis. The much lower levels of 2,6-xylidine produced from lidocaine (Fig. 13-8) do not produce this hematological toxicity. However, because of more rapid metabolism and the resultant shorter duration of action, overall toxicity of prilocaine is about 40% less than lidocaine. 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

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