Benzocaine Caffeine

Hays, P.A. Lurie, l.S. Quantitative analysis of adulterants in illicit heroin samples via reversed phase HPLC. J.Liq.Chromatogr., 1991, 14, 3513—3517 [simultaneous acetaminophen, acetylcodeine, ace-tylmorphine, benzocaine, caffeine, chloroquine, diamorphine, diazepam, diphenhydramine, dipyrone, lidocaine, methaqualone, monoacetylmorphine, morphine, nicotinamide, noscapine, papaverine, phe-nacetin, phenobarbital, phenolphthalein, N-phenyl-2-naphthylamine, salicylic acid, strychnine] Shen, J. Wanwimolruk, S. Clark, C.R. Roberts, M.S. A sensitive assay for aspirin and its metabolites using reversed-phase ion-pair high-performance liquid chromatography. J.Liq.Chromatogr., 1990,13, 751-761 [simultaneous metabolites gentisic acid, salicyluric acid LOD 50 ng/mL]... 

Simultaneous acetaminophen, acetylcodeine, benzocaine, caffeine, cocaine, diamorphine, lidocaine, 6-monoacetyhnorphine, morphine, noscapine, papaverine, procaine... 

Higuchi and Lachman [122] pioneered the approach of improving drug stability by complexation. They showed that aromatic esters can be stabilized in aqueous solutions in the presence of xanthines such as caffeine. Thus, the half-lives of benzocaine, procaine hydrochloride, and tetracaine are increased by approximately two- to fivefold in the presence of 2.5% caffeine. This increase in stability is attributed to the formation of a less reactive complex between caffeine and the aromatic ester. Professor K. A. Connors has written a comprehensive textbook that describes methods for the measurement of binding constants for complex formation in solution—along with discussions of pertinent thermodynamics, modeling statistics,... 

In a collaborative study on the quantitative determination of cocaine hydrochloride in powders and tablets that also contain other drugs (i.a. caffeine, procaine hydrochloride and benzocaine) as well as lactose, mannitol and starch, the free cocaine base was extracted with chloroform from an aqueous solution after addition of KjHPO. Tetracosane was added... 

Figure 18.13 Optimized chromatogram of a six-component mixture with acids and bases [reproduced with permission from Y. Hu and D.L. Massart, J. Chromatogr., 485, 311 (1989)]. Conditions column, 25cm x 4mm i.d. stationary phase, LiChrosorb RP18 5ixm mobile phase, 1 ml min methanol-phosphate buffer pH 3.0 (1 1) UV diode array detector. Peaks 1 = paracetamol 2 = acetylsalicylic acid 3 — caffeine 4 = benzocaine 5 = carbamazepine 6 = propyphenazone.

Stabilization of esters such as benzocaine (Fig. 120), procaine, and tetracaine by complex formation with caffeine was reported in the 1950s.513-515 The stabilization of drugs by caffeine is thought to result from the formation of stacking complexes. Thus, attack by water or hydroxide ion on the ester bonds of benzocaine is hindered when the benzocaine molecules are sandwiched between caffeine molecules. Similar stabilization by caffeine has been reported for base-catalyzed degradation of riboflavin.516... 

Figure 120. Stabilization of benzocaine by complex formation with caffeine (30°C, 0.04 N hydroxide ion). Caffeine concentration (1) 0.25% (2) 0.50% (3) 1.00% (4) 1.50% (5) 2.00% (6) 2.50%. (Reproduced from Ref. 5 13 with permission of the American Pharmaceutical Association.)...

T. Higuchi and L. Lachman, Inhibition of hydrolysis of esters in solution by formation of complexes I. Stabilization of benzocaine with caffeine, J. Am. Pharm. Assoc. 44,521-526(1955). 

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... 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, alprazolam, amitriptyline, amobarbital, amoxapine, antip3rrine, atropine, aza-tadine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorQrclizine, chlordiazepoxide, chlormezanone, cliloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazeptun, clonidine, clozapine, cocaine, codeine, colchicine, cgrclizine, cy-clobenzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem. 

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