Famotidine

Molecular formula: C8H15N7O2S3 Molecular weight: 337.4 CAS Registry No.: 76824-35-6

SAMPLE Matrix: blood Sample preparation: Condition an SPE cartridge with 1 mL MeOH and 1 mL water. Add 1 mL plasma to the SPE cartridge, wash with 5 mL water, elute with 2 mL MeCN. Evaporate the eluate, reconstitute in acetic acid/phosphate buffer, centrifuge, inject an aliquot. HPLC VARIABLES Guard column: Newguard RP-8 (Applied Biosystems) Column: Spherisorb C8 Mobile phase: MeCN: 30 mM pH 2.6 NaH2PO4 7:93 containing 7.2 mM triethylamine Flow rate: 1 Detector: UV 267 CHROMATOGRAM Retention time: 9.6 Limit of quantitation: 2 ng/mL KEYWORDS plasma; SPE; pharmacokinetics REFERENCE
Schwartz, J.I.; Yeh, K.C.; Berger, M.L.; Tomasko, L.; Hoover, M.E.; Ebel, D.L.; Stauffer, L.A.; Han, R.; Bjornsson, T.D. Novel oral medication delivery system for famotidine. J. CUn.Pharmacol., 1995, 35, 362-367

SAMPLE Matrix: blood Sample preparation: 1.5 mL Plasma + 100 |xL 4 M HCl, shake, add 8 mL diethyl ether, shake for 15 min, centrifuge at 1000 g at 4 for 5 min, discard ether layer. Add 0.5 mL saturated Na2CO3 solution, 0.5 mL saturated NaHCO3 solution, 100 JJLL 5 |xg/mL clopamide in water, and 7 mL ethyl acetate to aqueous layer, shake 15 min, centrifuge at 2000 g at 4 for 5 min, repeat extraction, combine organic layers and evaporate them to dryness under a stream of nitrogen at 37. Reconstitute with 150 jxL MeCN: water 12:88, vortex, inject 90 |xL aliquot. HPLCVARIABLES Column: 100 X 2 5 |xm ODS Hypersil C18 Mobile phase: MeCN: water 12:88 containing 20 mM Na2HPO4 and 50 mM sodium dodecyl sulfate adjusted to pH 3 with orthophosphoric acid Flow rate: 0.5 Injection volume: 90 Detector: UV 267 CHROMATOGRAM Retention time: 13 Internal standard: clopamide (9) Limit of detection: 5 ng/mL

OTHER SUBSTANCES Noninterfering: acetaminophen, amiloride, aspirin, atenolol, chlorothiazide, cimetidine, cyclopenthiazide, diazepam, furosemide, indapamide, labetalol, lorazepam, metoprolol, phenytoin, propranolol, ranitidine, salicylic acid, theophylline KEYWORDS plasma; microbore REFERENCE
Wanwimolruk, S.; Zoest, A.R.; Wanwimolruk, S.Z.; Hung, CT. Sensitive high-performance liquid chro matographic determination of famotidine in plasma. Application to pharmacokinetic study. J.Chromatogr., 1991, 572, 227-238

SAMPLE Matrix: blood Sample preparation: 1 mL Plasma + 1 mL saturated potassium carbonate + 5 mL ethyl acetate, mix, centrifuge. Remove the organic layer and add it to 1 mL saturated NaCl solution and 1 mL 1 M HCl, centrifuge. Remove the aqueous phase and add it to 1 mL saturated potassium carbonate solution and 3 mL ethyl acetate, extract. Remove a 2.5 mL aliquot of the organic layer and evaporate it to dryness under reduced pressure, reconstitute the residue with 400 jxL 250 JJIM phenanthrenequinone in MeOH, evaporate to dryness under reduced pressure, reconstitute with 40 (xL DMF and 40 uX. 2 M NaOH, heat at 60 for 15 min, cool on ice, neutralize with 5 M acetic acid, inject a 20 |xL aliquot. HPLC VARIABLES Column: reversed phase Mobile phase: MeCN: 10 mM pH 4 citrate buffer 40:50 Flow rate: 1 Injection volume: 20 Detector: F ex 296 em 411 CHROMATOGRAM Limit of detection: 5 ng/mL KEYWORDS plasma; pharmacokinetics; derivatization REFERENCE
Echizen, H.; Shoda, R.; Umeda, N.; Ishizaki, T. Plasma famotidine concentration versus intragastric pH in patients with upper gastrointestinal bleeding and in healthy subjects. CUn.Pharmacol.Then, 1988, 44, 690-698

SAMPLE Matrix: blood, urine Sample preparation: 50 JJLL Plasma or urine + 350 |xL 0.2 jxg/mL 3-butylxanthine in MeOH, centrifuge at 6000 g for 5 min. Evaporate supernatant under a stream of nitrogen at 40, reconstitute in 250 JULL mobile phase, inject an aliquot. HPLCVARIABLES Column: 250 X 4.2 Cosmosil 5C18 Mobile phase: MeCN: 30 mM pH 7.0 phosphate buffer 10:90 Flow rate: 1.5 Detector: UV 267

CHROMATOGRAM Internal standard: 3-butylxanthine Limit of quantitation: 100 ng/mL KEYWORDS plasma REFERENCE
Hasegawa, T.; Nadai, M.; Wang, L.; Takayama, Y.-L; Kato, K.; Nabeshima, T.; Kato, N. Renal excretion of famotidine and role of adenosine in renal failure induced by bacterial lipopolysaccharide in rats. DrugMetab.Dispos., 1994, 22, 8-13

SAMPLE Matrix: formulations Sample preparation: Inject a 20 JJLL aliquot. HPLCVARIABLES Column: Nova Pak C18 Mobile phase: MeCN:0.1% acetic acid: 10 mM pH 7.8 (NH4)H2PO4 10:23:74 Flow rate: 1 Injection volume: 20 Detector: UV 300 CHROMATOGRAM Retention time: 13.9 OTHER SUBSTANCES Simultaneous: cefmetazole Noninterfering: degradation products KEYWORDS stability-indicating; injections; 5% dextrose REFERENCE
Lee, D.K.T.; Wong, C-Y; Wang, D.-R; Chang, L.-C; Wu, K.-H. Stability of cefmetazole sodium and famotidine. Am.J.Health-Syst.Pharm., 1996, 53, 432-442

SAMPLE Matrix: formulations Sample preparation: Dilute with 5% dextrose (if necessary), inject a 20 jxL aliquot. HPLCVARIABLES Column: Nova Pak C18 Mobile phase: MeOH: 100 mM (NH4)2HPO4 20:80, pH 7.80 Flow rate: 1 Injection volume: 20 Detector: UV 322 CHROMATOGRAM Retention time: 4.6 OTHER SUBSTANCES Simultaneous: cefazolin

KEYWORDS

injections; 5% dextrose; stability-indicating

REFERENCE
Wang, D.-P.; Chang, L.-C; Wong, C-Y; Lee, D.K.T. Stability of cefazolin sodium-famotidine admixture. Am.J.Hosp.Pharm., 1994, 51, 2205-2209

SAMPLE

Matrix: formulations Sample preparation: Shake, remove 2 mL of oral suspension, dilute to 40 mL with water, vortex 1 min, centrifuge at 2000 rpm for 10 min. Dilute a 100 |xL aliquot of supernatant with 100 |xL of 100 |xg/mL theophylline and add 800 |xL water, inject 20 |JLL aliquot.
HPLCVARIABLES

Column: 300 mm 10 |xm Waters reversed-phase C18 Mobile phase: MeCN: 50 mM sodium acetate buffer 8:92, adjusted to pH 6.5 Flow rate: 1.5 Injection volume: 20 Detector: UV 254
CHROMATOGRAM

Retention time: 5.6 Internal standard: theophylline (4.3)

KEYWORDS

stability-indicating
REFERENCE
Quercia, R.A.; Jay, G.T.; Fan, C; Chow, M.S. Stability of famotidine in an extemporaneously prepared oral liquid. Am.J.Hosp.Pharm., 1993, 50, 691-693

SAMPLE Matrix: solutions

HPLC VARIABLES

Column: 250 X 4.6 5 ixm octadecylsilane (Beckman) Mobile phase: MeOH:MeCN:glacial acetic acid: 10 mM KH2PO4 12:3:0.1:84.9, pH 5.0 Flow rate: 1 Detector: UV 266
REFERENCE
Junnarkar, G.H.; Stavchansky, S. Isothermal and nonisothermal decomposition of famotidine in aqueous solution. Pharm.Res., 1995, 12, 599-604

SAMPLE Matrix: solutions

HPLCVARIABLES

Column: 150 X 4.6 12 |xm l-m3o-istoyl-2-[(13-carboxyl)-tridecoyl]-sn-3-glycerophosphocholine chemically bonded to silica (Regis) Mobile phase: MeCN: 100 mM pH 7.0 phosphate buffer 20:80 Flow rate: 1 Detector: UV 254

CHROMATOGRAM Retention time: k/ 0.54 OTHER SUBSTANCES Also analyzed: acebutolol, alprenolol, antazoline, atenolol, betaxolol, bisoprolol, bopindolol, bupranolol, carteolol, celiprolol, chloropyramine, chlorpheniramine, cicloprolol, cimetidine, cinnarizine, cirazoline, clonidine, dilevalol, dimethindene, diphenhydramine, doxazosin, esmolol, isothipendyl, ketotifen, metiamide, metoprolol, moxonidine, nadolol, naphazoline, nifenalol, nizatidine, oxprenolol, pheniramine, phentolamine, pindolol, pizotyline (pizotifen), practolol, prazosin, promethazine, propranolol, pyrilamine (mepyramine), ranitidine, roxatidine, sotalol, tiamenidine, timolol, tramazoline, tripelennamine, triprolidine, tymazoline, UK-14,304 REFERENCE
Kaliszan, R.; Nasal, A.; Turowski, M. Binding site for basic drugs on c^-acid glycoprotein as revealed by chemometric analysis of biochromatographic data. Biomed.Chromatogr., 1995, 9, 211-215

SAMPLE Matrix: solutions HPLC VARIABLES Column: 250 X 4.6 Zorbax RX Mobile phase: Gradient. A was 10 mL concentrated orthophosphoric acid and 7 mL triethylamine in 1 L water. B was 10 mL concentrated orthophosphoric acid and 7 mL triethylamine in 200 mL water, make up to 1 L with MeCN. A:B from 100:0 to 0:100 over 30 min, maintain at 0:100 for 5 min. Column temperature: 30 Flow rate: 2 Detector: UV 210 OTHER SUBSTANCES Also analyzed: acepromazine, acetaminophen, acetophenazine, albuterol, aminophylline, amitriptyline, amobarbital, amoxapine, amphetamine, amylocaine, antipyrine, aprobarbital, aspirin, atenolol, atropine, avermectin, barbital, benzocaine, benzoic acid, benzotropine, benzphetamine, berberine, bibucaine, bromazepan, brompheniramine, buprenorphine, buspirone, butabarbital, butacaine, butethal, caffeine, carbamazepine, carbromal, chloramphenicol, chlordiazepoxide, chloroquine, chlorothiazide, chloroxylenol, chlorphenesin, chlorpheniramine, chlorpromazine, chlorpropamide, chlortetracycline, cimetidine, cinchonidine, cinchonine, clenbuterol, clonazepam, clonixin, clorazepate, cocaine, codeine, colchicine, cortisone, coumarin, cyclazocine, cyclobenzaprine, cyclothiazide, cyheptamide, cymarin, danazol, danthron, dapsone, debrisoquine, desipramine, dexamethasone, dextromethorphan, dextropropoxyphene, diamorphine, diazepam, diclofenac, diethylpropion, diethylstilbestrol, diflunisal, digitoxin, digoxin, diltiazem, diphenhydramine, diphenoxylate, diprenorphine, dipyrone, disulfiram, dopamine, doxapram, doxepin, dronabinol, ephedrine, epinephrine, epinine, estradiol, estriol, estrone, ethacrynic acid, ethosuximide, etonitazene, etorphine, eugenol, fenbendazole, fencamfamine, fenoprofen, fenproporex, fentanyl, flubendazole, flufenamic acid, flunitrazepam, 5-fluorouracil, fluoxymesterone, fluphenazine, furosemide, gentisic acid, gitoxigenin, glipizide, glunixin, glutethimide, glybenclamide, guaiacol, halazepam, haloperidol, hydrochlorothiazide, hydrocodone, hydrocortisone, hydromorphone, hydroxyquinoline, ibogaine, ibuprofen, iminostilbene, imipramine, indomethacin, isocarbostyril, isocarboxazid, isoniazid, isoproterenol, isoxsuprine, ivermectin, ketamine, ketoprofen, kynurenic acid, levorphanol, lidocaine, lorazepam, lormetazepam, loxapine, mazindol, mebendazole, meclizine, meclofenamic acid, medazepam, mefenamic acid, megestrol, mepacrine, meperidine, mephentermine, mephenytoin, mephesin, mephobarbital, mepivacaine, mescaline, mesoridazine, methadone, methamphetamine, methapyrilene, methaqualone, methazolamide, methocarbamol, methoxamine, methsuximide, methyl salicylate, methyldopa, methyldopamine, methylphenidate, meth-

ylprednisolone, methyltestosterone, methyprylon, mei prolol, mibolerone, morphine, nadolol, nalorphine, naloxone, naltrexone, naphazoline, naproxen, nefopam, niacinamide, nicotine, nicotinic acid, nifedipine, niflumic acid, nitrazepam, norepinephrine, nortriptyline, noscapine, nylidrin, oxazepam, oxycodone, oxymorphone, oxyphenbutazone, oxytetracycline, papaverine, pargyline, pemoline, pentazocine, pentobarbital, persantine, phenacetin, phenazocine, phenazopyridine, phencyclidine, phendimetrazine, phenelzine, pheniramine, phenobarbital, phenothiazine, phensuximide, phentermine, phenylbutazone, phenylephrine, phenylpropanolamine, piperocaine, prazepam, prednisolone, primidone, probenecid, progesterone, propiomazine, propranolol, propylparaben, pseudoephedrine, puromycin, pyrilamine, pyrithyldione, quazepam, quinaldic acid, quinidine, quinine, ranitidine, recinnamine, reserpine, resorcinol, saccharin, albuterol, salicylamide, salicylic acid, scopolamine, scopoletin, secobarbital, strychnine, sulfacetamide, sufadiazine, sulfadimethoxine, sulfaethidole, sulfamerazine, sulfamethazine, sulfamethoxizole, sulfanilamide, sulfapyridine, sulfasoxizole, sulindac, tamoxifen, temazepam, testosterone, tetracaine, tetracycline, tetramisole, thebaine, theobromine, theophylline, thiabendazole, thiamine, thiamylal, thiobarbituric acid, thioridazine, thiosalicylic acid, thiothixene, thymol, tolazamide, tolazoline, tobutamide, tolmetin, tranylcypromine, triamcinolone, tribenzylamine, trichloromethiazide, trifluoperazine, trihexyphenidyl, trimethoprim, tripelennamine, triproilidine, tropacocaine, tyramine, verapamil, vincamine, warfarin, yohimbine, zoxazolamine REFERENCE
Hill, D.W.; Kind, A. J. Reversed-phase solvent gradient HPLC retention indexes of drugs. J. Anal.Toxicol., 1994, 18, 233-242

ANNOTATED BIBLIOGRAPHY

Qin, X.Z.; Ip, D.P.; Chang, K.H.; Dradransky, P.M.; Brooks, M.A.; Sakuma, T. Pharmaceutical application of LC-MS. 1-Characterization of a famotidine degradate in a package screening study by LC-APCI MS. J.Pharm.Biomed.AnaL, 1994, 12, 221-233 Kamath, B.V.; Shivram, K.; Newalkar, B.L.; Shah, A.C. Liquid chromatographic analysis and degradation kinetics of famotidine. J.Liq.Chromatogr., 1993, 16, 1007-1014 [tablets; stability indicating] Imai, Y.; Kobayashi, S. A simple method for the quantification of famotidine in human plasma and urine by paired-ion high performance liquid chromatography. Biomed.Chromatogr., 1992, 6, 222-223 Cvitkovic, L.; Zupancic-Kralj, L.; Marsel, J. Determination of famotidine in human plasma and urine by high-performance liquid chromatography. J.Pharm.Biomed.AnaL, 1991, 9, 207-210 Guo, P.; Ye, L.M.; Lu, B.; He, Y. J.; Li, Z.W. [Direct injection of plasma to determine famotidine in plasma using HPLC column switching technique]. Yao Hsueh Hsueh Pao, 1990, 25, 622-625 Bullock, L.; Fitzgerald, J.R; Glick, M.R. Stability of famotidine 20 and 50 mg/L in total nutrient admixtures. Am.J.Hosp.Pharm., 1989, 46, 2326-2329 [theophylline (IS)] Bullock, L.; Fitzgerald, J.F.; Glick, M.R.; Parks, R.B.; Schnabel, J.G.; Hancock, B.G. Stability of famotidine 20 and 40 mg/L and amino acids in total parenteral nutrient solutions. Am.J.Hosp.Pharm., 1989, 46, 2321-2325 [stability-mdicating; theophylline (IS)] DiStefano, J.E.; Mitrano, F.P.; Baptista, R.J.; Der, M.M.; Silvestri, A.P.; Palombo, J.D.; Bistrian, B.R. Long-term stability of famotidine 20 mg/L in a total parenteral nutrient solution. Am.J.Hosp.Pharm., 1989, 46, 2333-2335 [non-interfering degradation products]