Nizatidine

Molecular formula: C12H2IN5O2S2

Molecular weight: 331.5
CAS Registry No.: 76963-41 -2

SAMPLE
Matrix: blood
Sample preparation: 2 mL Whole blood or plasma + 2 mL buffer + 5 mL chloroform:
isopropanol: n-heptane 60:14:26, shake gently horizontally for 10 min, centrifuge at 2800
g for 10 min. Remove the lower organic layer and evaporate it to dryness under vacuum
at 45, reconstitute the residue in 100 |xL mobile phase, centrifuge at 2800 g for 5 min,
inject a 50 |xL aliquot of the supernatant. (Buffer was saturated ammonium chloride
solution 25% diluted with water, adjusted to pH 9.5 with 25% ammonia solution.)
HPLCVARIABLES
Column: 300 X 3.9 4 ^m NovaPack C18
Mobile phase: MeOH:THF:buffer 65:5:30 (Buffer was 0.68 g/L (10 mM (sic)) KH2PO4
adjusted to pH 2.6 with concentrated orthophosphoric acid.) (At the end of each session
wash the column with water for 1 h and MeOH for 1 h, re-equilibrate for 30 min.)
Column temperature: 30
Flow rate: 0.8
Injection volume: 50
Detector: UV 322
CHROMATOGRAM
Retention time: 3.52
Limit of detection: <120 ng/mL
OTHER SUBSTANCES
Extracted: acebutolol, acenocoumarol, acepromazine, aceprometazine, acetaminophen,
aconitine, ajmaline, albuterol, alimemazine, alminoprofen, alpidem, alprazolam, alprenolol, amitriptyline, amodiaquine, amoxapine, aspirin, astemizole, atenolol, benazepril,
benperidol, benzoylecgonine, bepridil, betaxolol, bisoprolol, bromazepam, brompheniramine, bumadizone, bupivacaine, buprenorphine, buspirone, caffeine, carbamazepine,
carbinoxamine, carpipramine, celiprolol, cetirizine, chlorambucil, chlordiazepoxide,
chlormezanone, chlorophenacinone, chloroquine, chlorpheniramine, chlorpromazine,
chlorpropamide, cibenzoline, cicletanine, clemastine, clobazam, clomipramine, clonazepam, clonidine, clorazepate, clozapine, cocaine, colchicine, cyamemazine, cyclizine, cycloguanil, cyproheptadine, cytarabine, dacarbazine, daunorubicin, debrisoquine, demexiptiline, desipramine, dextromethorphan, dextromoramide, dextropropoxyphene, diazepam,
diazoxide, diclofenac, dihydralazine, diltiazem, diphenhydramine, dipyridamole, disopyramide, dosulepine, doxepin, doxylamine, droperidol, ephedrine, estazolam, etodolac, fenfluramine, fenoprofen, fentiazac, flecainide, floctafenine, flumazenil, flunitrazepam, fluoxetine, fluphenazine, flurbiprofen, fluvoxamine, glibenclamide, glibornuride, glipizide,
glutethimide, haloperidol, histapyrrodine, hydroxychloroquine, hydroxyzine, ibuprofen,
imipramine, indomethacin, iproniazid, ketamine, ketoprofen, labetalol, levomepromazine,
lidocaine, lidoflazine, loperamide, loprazolam, loratadine, lorazepam, loxapine, maprotiline, medazepam, medifoxamine, mefenamic acid, mefenidramine, mefloquine, melphalan,
meperidine, mephentermine, mepivacaine, metapramine, metformin, methadone, methaqualone, methocarbamol, methotrexate, metipranolol, metoclopramide, metoprolol, mexiletine, mianserine, midazolam, minoxidil, moclobemide, moperone, morphine, nadolol,
nalbuphine, naproxen, nialamide, nicardipine, nifedipine, niflumic acid, nimodipine, nitrazepam, nitrendipine, nomifensine, nortriptyline, omeprazole, opipramol, oxazepam, oxprenolol, penbutolol, penfluridol, pentazocine, phencyclidine, phenobarbital, phenol, phenylbutazone, pimozide, pindolol, pipamperone, piroxicam, prazepam, prazosin, prilocaine,

procainamide, procarbazine, proguanil, promethazine, propafenone, propranolol, protriptyline, pyrimethamine, quinidine, quinine, quinupramine, ramipril, ranitidine, reserpine,
secobarbital, strychnine, sulfinpyrazole, sulindac, sulpride, suriclone, temazepam, tenoxicam, terbutaline, terfenadine, tetracaine, tetrazepam, thiopental, thioproperazine, thioridazine, tianeptine, tiapride, tiaprofenic acid, ticlopidine, timolol, tioclomarol, tofisopam,
tolbutamide, toloxatone, trazodone, triazolam, trifluoperazine, trifluperidol, trimipramine, triprolidine, tropatenine, verapamil, viloxazine, vinblastine, vincristine, vindesine,
warfarin, yohimbine, zolpidem, zopiclone, zorubicine
Interfering: amisulpride, benzocaine, carteolol, codeine, lisinopril, mephenesin, nalorphine, naloxone, naltrexone, nizatidine, ritodrine, sotalol, sultopride
KEYWORDS
whole blood; plasma
REFERENCE
Tracqui, A.; Kintz, P.; Mangin, P. Systematic toxicological analysis using HPLC/DAD. J.Forensic ScL,
1995, 40, 254-262

SAMPLE
Matrix: blood, saliva, urine
Sample preparation: Plasma or saliva. 1 mL Plasma or saliva + 200 ng IS + 250 /JLL
saturated sodium carbonate + 500 jxL saturated solution of sodium sulfate in EtOH,
extract into 5 mL dichloromethane. Evaporate the organic layer and dissolve the residue
in 200 MJL 100 mM HCl.mobile phase 1:1, inject an aliquot. Urine. 1 mL Urine + 2000
ng IS + 1 mL saturated sodium carbonate, extract into 5 mL dichloromethane. Evaporate
the organic layer and dissolve the residue in 200 jxL mobile phase, inject an aliquot.
HPLC VARIABLES
Guard column: Brownlee Spheri-10 RP-8 guard column
Column: 250 X 4.6 6 |xm Zorbax C8
Mobile phase: MeCN containing 1% triethylamine: 20 mM ammonium acetate 18.5:81.5
Flow rate: 1
Detector: UV 313
CHROMATOGRAM
Internal standard: Nl-ethylnizatidine
Limit of detection: 10 ng/mL
KEYWORDS
plasma
REFERENCE
Knadler, M.P.; Bergstrom, R.F.; Callaghan, J.T.; Rubin, A. Nizatidine, an H2-blocker. Its metabolism and
disposition in man. Drug Metab.Dispos., 1986, 14, 175-182

SAMPLE
Matrix: blood, tissue
Sample preparation: Blood. 25 |JLL Plasma + 100 jxL water + 100 |xL 5 M NaOH + 5mL
dichloromethane, shake for 10 min, centrifuge at 1650 g for 10 min. Remove 4 mL of the
organic layer and evaporate it to dryness under reduced pressure at room temperature,
reconstitute the residue in 100 |xL mobile phase, inject a 50 |JLL aliquot. (Hemolyze 25 |xL
whole blood with 200 |xL water then proceed as above.) Tissue. Homogenize brain tissue
with 100 |xL water and 1 mL saline at 0 for 1 min, add 100 |xL 500 mM NaOH, extract
with 5 mL dichloromethane. Remove 3 mL of the organic layer and evaporate it to dryness, reconstitute the residue in 100 |xL mobile phase, centrifuge at 10000 g, inject a 50
(JLL aliquot.

HPLCVARIABLES
Column: 250 X 4 Senshu gel 7C18H (Senshu, Tokyo)
Mobile phase: MeCN: buffer 5:95. (Buffer was 5 mM NaH2PO4 containing 5 mM tetramethylammonium chloride.)
Column temperature: 30
Flow rate: 2
Injection volume: 50
Detector: UV 320
CHROMATOGRAM
Internal standard: nizatidine
OTHER SUBSTANCES
Extracted: ranitidine
KEYWORDS
nizatidine is IS; plasma; mouse; brain; whole blood
REFERENCE
Shimokawa, M.; Yamamoto, K.; Kawakami, J.; Sawada, Y; Iga, T. Effect of renal or hepatic dysfunction
on neurotoxic convulsion induced by ranitidine in mice. Pharm.Res., 1994, 11, 1519-1523

SAMPLE
Matrix: formulations
Sample preparation: Dilute a 1 mL aliquot to a theoretical concentration of 30 |xg/mL
with MeCN: water 2:50, inject a 20 u-L aliquot.
HPLC VARIABLES
Column: 150 mm long 5 |xm Waters Resolve C18
Mobile phase: MeOH: 100 mM ammonium acetate: diethylamine 1280:2720:4, adjusted to
a pH of 7.5
Column temperature: 30
Flow rate: 1
Injection volume: 20
Detector: UV 230
CHROMATOGRAM
Retention time: 6.7
OTHER SUBSTANCES
Simultaneous: nizatidine amide, nizatidine sulfoxide, phenol
KEYWORDS
injections; stability-indicating
REFERENCE
Raineri, D.L.; Cwik, M.J.; Rodvold, K.A.; Deyo, K.L.; Scaros, L.P.; Fischer, J.H. Stability of nizatidine
in commonly used intravenous fluids and containers. Am.J.Hosp.Pharm., 1988, 45, 1523-1529

SAMPLE
Matrix: perfusate, urine
Sample preparation: Urine. Take 10 \xL urine diluted 10 times with 10 mM pH 7.5
Na2HPO4 buffer, make up volume to 300 |JLL with 10 mM pH 7.5 Na2HPO4 buffer. Place
solution on YM-10 ultrafiltration membrane with a cut-off of 10000, centrifuge at 4000 g
for 20 min. Mix 180 |xL filtrate with 20 |JLL MeOH, inject 50 |JLL. Perfusate. Take 10-100

|xL perfusate, make up volume to 300 |xL with 10 mM pH 7.5 Na2HPO4 buffer. Place
solution on YM-IO ultrafiltration membrane with a cut-off of 10000, centrifuge at 4000 g
for 20 min. Mix 180 ^L filtrate with 20 JJIL MeOH, inject 50 |xL.
HPLCVARIABLES
Guard column: 75 X 2.1 5 |xm LiChrosorb RP-18
Column: 150 X 4.6 5 |xm LiChrosorb RP-18
Mobile phase: MeOH: 10 mM pH 7.5 Na2HPO4 30:70
Column temperature: 40
Flow rate: 1
Injection volume: 50
Detector: UV 228
CHROMATOGRAM
Retention time: 10
Internal standard: nizatidine
Limit of detection: 50 ng/mL
OTHER SUBSTANCES
Extracted: cimetidine
KEYWORDS
nizatidine is IS
REFERENCE
Boom, S.P.A.; Moons, M.M.; Russel, F.G.M. Renal tubular transport of cimetidine in the isolated perfused
kidney of the rat. Drug Metab.Dispos., 1994, 22, 148-153

SAMPLE
Matrix: solutions
HPLCVARIABLES
Column: 150 X 4.6 12 |xm l-myristoyl-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' 0.43
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, famotidine, isothipendyl, ketotifen, metiamide, metoprolol, moxonidine,
nadolol, naphazoline, nifenalol, 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 Ct1-acid glycoprotein as revealed by
chemometric analysis of biochromatographic data. Biomed.Chromatogr., 1995, 9, 211-215

SAMPLE

Matrix: solutions
HPLCVARIABLES
Column: 250 X 4.6 5 |xm Supelcosil LC-DP (A) or 250 X 4 5 |xm LiChrospher 100 RP-8 (B)
Mobile phase: MeCN:0.025% phosphoric acid:buffer 25:10:5 (A) or 60:25:15 (B) (Buffer
was 9 mL concentrated phosphoric acid and 10 mL triethylamine in 900 mL water, adjust
pH to 3.4 with dilute phosphoric acid, make up to 1 L.)

Flow rate: 0.6

Injection volume: 25
Detector: UV 229
CHROMATOGRAM
Retention time: 5.57 (A), 3.13 (B)
OTHER SUBSTANCES
Also analyzed: acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine,
albuterol, alprazolam, amitriptyline, amobarbital, amoxapine, antipyrine, atenolol, atropine, azatadine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam,
bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine,
chlorcyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine,
chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, cyclizine, cyclobenzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal,
diltiazem, diphenhydramine, diphenidol, diphenoxylate, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine,
fenoprofen, fentanyl, fiavoxate, fluoxetine, fiuphenazine, flurazepam, flurbiprofen, fluvoxamine, furosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydroxychloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac,
labetalol, levorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol,
mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol,
metformin, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine,
methoxamine, methyldopa, methylphenidate, metoclopramide, metolazone, metoprolol,
metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, norepinephrine, nortriptyline, oxazepam, oxycodone,
oxymetazoline, 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,
thiethylperazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide,
tolmetin, '.razodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine,
zopiclone
KEYWORDS
some details of plasma extraction
REFERENCE
Koves, E.M. Use of high-performance liquid chromatography-diode array detection in forensic toxicology.
J.ChromatogrA, 1995, 692, 103-119