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Ranitidine

Molecular formula: C13H22N4O3S


Molecular weight: 314.4
CAS Registry No.: 66357-35-5, 66357-59-3 (HCI)

SAMPLE
Matrix: blood
Sample preparation: 1 mL Plasma + 25 fxL 10 (xg/mL procainamide in MeOH + 15 |xL
6 M NaOH + 2 mL ethyl acetate: isopropanol 96:4, shake mechanically for 20 min, cen-
trifuge at 3000 rpm for 10 min. Remove the organic layer and evaporate it to dryness
under a stream of nitrogen at 40, reconstitute the residue in 100 |xL MeOH, inject a 75
JULL aliquot.

HPLCVARIABLES
Column: 150 X 3.9 10 |mm ixBondapak C18
Mobile phase: MeCN: 10 mM pH 5.1 KH2PO4 8:92
Flow rate: 2.5
Injection volume: 75
Detector: UV 330

CHROMATOGRAM
Retention time: 5
Internal standard: procainamide (3)
Limit of detection: 20 ng/mL

OTHER SUBSTANCES
Simultaneous: lidocaine
Noninterfering: brompheniramine, chlorpheniramine, cimetidine, diazepam, diclofenac,
glyburide, ibuprofen, ketoprofen, metoclopramide, naproxen, phenylbutazone, verapamil

KEYWORDS
plasma; pharmacokinetics

REFERENCE
al-Khamis, K.I.; El-Sayed, Y.M.; Al-Rashood, K.A.; Bawazir, S.A. High-performance liquid chromato-
graphic determination of ranitidine in human plasma. J.Liq.Chromatogr., 1995, 18, 277-286

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 jxL 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 fxm 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: 3.38
Limit of detection: <120 ng/mL

OTHER SUBSTANCES
Extracted: acebutolol, acenocoumarol, acepromazine, aceprometazine, acetaminophen,
aconitine, ajmaline, alimemazine, alminoprofen, alpidem, alprazolam, alprenolol, ami-
triptyline, amodiaquine, amoxapine, astemizole, benazepril, benperidol, benzocaine, ben-
zoylecgonine, bepridil, betaxolol, bisoprolol, bromazepam, brompheniramine, bumadizone,
bupivacaine, buprenorphine, buspirone, caffeine, carbamazepine, carbinoxamine, carpi-
pramine, carteolol, celiprolol, cetirizine, chlorambucil, chlordiazepoxide, chlorophena-
cinone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, cibenzoline, ci-
cletanine, clemastine, clobazam, clomipramine, clonazepam, clonidine, clorazepate,
clozapine, cocaine, colchicine, cyamemazine, cyclizine, cycloguanil, cyproheptadine, cytar-
abine, dacarbazine, daunorubicin, debrisoquine, demexiptiline, desipramine, dextrome-
thorphan, dextromoramide, dextropropoxyphene, diazepam, diazoxide, diclofenac, dihy-
dralazine, diltiazem, diphenhydramine, dipyridamole, disopyramide, dosulepine, doxepin,
doxylamine, droperidol, ephedrine, estazolam, etodolac, fenfluramine, fenoprofen, fentia-
zac, flecainide, floctafenine, flumazenil, flunitrazepam, fluoxetine, fluphenazine, flurbipro-
fen, fluvoxamine, glibenclamide, glibornuride, glipizide, glutethimide, haloperidol, hista-
pyrrodine, hydroxychloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin,
iproniazid, ketamine, ketoprofen, labetalol, levomepromazine, lidocaine, lidoflazine, lisi-
nopril, loperamide, loprazolam, loratadine, lorazepam, loxapine, maprotiline, medazepam,
medifoxamine, mefenamic acid, mefenidramine, mefloquine, melphalan, meperidine, me-
phenesin, mephentermine, mepivacaine, metapramine, methadone, methaqualone, meth-
ocarbamol, methotrexate, metipranolol, metoclopramide, metoprolol, mexiletine, mian-
serine, midazolam, minoxidil, moclobemide, moperone, nadolol, nalbuphine, nalorphine,
naloxone, naltrexone, naproxen, nialamide, nicardipine, nifedipine, niflumic acid, nimo-
dipine, nitrazepam, nitrendipine, nizatidine, nomifensine, nortriptyline, omeprazole, op-
ipramol, oxazepam, oxprenolol, penbutolol, penfluridol, pentazocine, phencyclidine, phen-
ylbutazone, pimozide, pindolol, pipamperone, piroxicam, prazepam, prazosin, prilocaine,
procainamide, procarbazine, proguanil, promethazine, propafenone, propranolol, protrip-
tyline, pyrimethamine, quinidine, quinine, quinupramine, ramipril, reserpine, secobar-
bital, sotalol, strychnine, sulfinpyrazole, sulindac, sulpride, suriclone, temazepam, ten-
oxicam, terfenadine, tetracaine, tetrazepam, thiopental, thioproperazine, thioridazine,
tianeptine, tiaprofenic acid, ticlopidine, timolol, tioclomarol, tofisopam, tolbutamide, tra-
zodone, triazolam, trifluoperazine, trifluperidol, trimipramine, triprolidine, tropatenine,
verapamil, viloxazine, vinblastine, vincristine, vindesine, warfarin, yohimbine, zolpidem,
zopiclone, zorubicine
Interfering: albuterol, amisulpride, aspirin, atenolol, chlormezanone, codeine, metformin,
morphine, phenobarbital, phenol, ritodrine, sultopride, terbutaline, tiapride, toloxatone

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
Sample preparation: Mix plasma with sodium carbonate solution and extract twice with
3 mL dichloromethane. Remove the organic layer and evaporate it to dryness, reconstitute
the residue in 100 |xL mobile phase, inject a 40 |xL aliquot.
HPLCVARIABLES
Column: 150 X 3.6 ODS Hypersil
Mobile phase: MeCN:isopropanol:pH 7 sodium acetate buffer:water 21:6:20:53
Flow rate: 0.4
Injection volume: 40
Detector: UV 280

CHROMATOGRAM
Limit of detection: 20 ng/mL
OTHER SUBSTANCES
Noninterfering: diclofenac

KEYWORDS
plasma
REFERENCE
Van Gelderen, M.E.M.; Oiling, M.; Barends, D.M.; Meulenbelt, J.; Salomons, P.; Rauws, A.G. The bio-
availability of diclofenac from enteric coated products in healthy volunteers with normal and artifi-
cially decreased gastric acidity. Biopharm.Drug Dispos., 1994, 15, 775788

SAMPLE
Matrix: blood
Sample preparation: Condition a 100 mg Bond Elut CN cartridge with 3 mL water, 3 mL
MeOH, and 3 mL 50 mM pH 7.0 sodium phosphate buffer. Mix 4 volumes of plasma with
1 volume of 100 mM NaH2PO4. Add 0.5-1 mL plasma to the SPE cartridge, wash with 5
mL water, elute with 1 mL MeOH. Evaporate the eluate to dryness, reconstitute in 120
JiL phosphate buffer, inject a 100 jxL aliquot.

HPLCVARIABLES
Column: 300 X 3.9 10 jxm jjiBondapak C18
Mobile phase: MeOH: 50 mM pH 7.0 sodium phosphate buffer 60:40
Flow rate: 0.8
Injection volume: 100
Detector: UV 315

CHROMATOGRAM
Retention time: 8
Limit of detection: 1 ng/mL

KEYWORDS
plasma; SPE; pharmacokinetics
REFERENCE
Biermann, B.; Sommer, N.; Winne, D.; Schumm, F.; Maier, U.; Breyer-Pfaff, U. Renal clearance of pyr-
idostigmine in myasthenic patients and volunteers under the influence of ranitidine and pirenzepine.
Xenobiotica, 1993,23, 1263-1275

SAMPLE
Matrix: blood
Sample preparation: Condition a 100 mg LRC Bond Elut unendcapped cyanopropyl SPE
cartridge with 1 mL MeOH and 1 mL water. 1 mL Serum or plasma + 250 jxL 2 |xg/mL
procainamide in buffer, vortex, centrifuge at 1300 rpm for 10 min (plasma only), add 1
mL sample to the SPE cartridge, wash twice with 1 mL water, dry with nitrogen for 30
s, elute with two 250 |JLL aliquots of MeOH: buffer 60:40, inject 100 |xL aliquot of eluate.
(Buffer was 50 mM KH2PO4 and Na2HPO4 50:50 v/v adjusted to pH 6.0 with phosphoric
acid.)

HPLCVARIABLES
Guard column: 15 X 4.6 7 jim Brownlee RP-18
Column: 250 X 4.6 5 |xm Spherisorb ODS-I
Mobile phase: MeOH:THF:buffer 65:5:30 (Buffer was 50 mM KH2PO4 and Na2HPO4
50:50 v/v adjusted to pH 6.0 with phosphoric acid.)
Column temperature: 48
Flow rate: 1.25
Injection volume: 100
Detector: UV 320

CHROMATOGRAM
Retention time: 4.5
Internal standard: procainamide (5.4)
Limit of quantitation: 10 ng/mL

KEYWORDS
serum; plasma; robotic sample preparation; SPE

REFERENCE
Lloyd, T.L.; Perschy, T.B.; Gooding, A.E.; Tomlinson, J.J. Robotic solid phase extraction and high per-
formance liquid chromatographic analysis of ranitidine in serum or plasma. Biomed.Chromatogr.,
1992, 6, 311-316

SAMPLE
Matrix: blood
Sample preparation: 1 mL Plasma + 200 |xL MeCN + 50 mg ZnSO4, vortex for 2 min,
centrifuge at 2200 g for 3 min. Remove the supernatant, filter (0.45 |xm), inject an aliquot.
(Tubes were cleaned by sonication with acetone for 30 min, sonication twice with MeCN
for 15 min, and drying at 100. Stir 100 g ZnSO4 crystals with 200 mL MeCN for 30 min,
decant MeCN, repeat twice with fresh MeCN, dry crystals in a hood at room temperature.)

HPLCVARIABLES
Column: 50 X 4.1 Alltech PLRP-S
Mobile phase: MeCN: 5 mM K2HPO4 + 0.5 mM tetraethylammonium hydroxide 20:80, pH
11
Flow rate: 1
Detector: UV 315

CHROMATOGRAM
Retention time: 7
Limit of quantitation: 5 ng/mL

OTHER SUBSTANCES
Simultaneous: metabolites
Noninterfering: acetaminophen, ampicillin, cimetidine, creatinine, tetracycline

KEYWORDS
plasma

REFERENCE
Rustum, A.M. Rapid and sensitive HPLC determination of ranitidine in plasma. Application to phar-
macokinetics study. J.Liq.Chromatogr., 1988, 11, 2315-2335
SAMPLE
Matrix: blood, milk
Sample preparation: 100 |xL Serum or whole milk + 25 |xL MeOH + 4 mL dichlorome-
thane, vortex, centrifuge. Remove the organic layer and evaporate it to dryness under a
stream of nitrogen, reconstitute the residue in 200 jxL mobile phase, inject a 50 JULL
aliquot.

HPLCVARIABLES
Guard column: 15 X 3.2 RP-18 (Applied Biosystems)
Column: 300 X 3.9 ixBondapak C18
Mobile phase: MeCN: water: glacial acetic acid: triethylamine 15:85:0.15:0.02
Flow rate: 1
Injection volume: 50
Detector: UV 228
CHROMATOGRAM
Retention time: 10.7
Internal standard: ranitidine

OTHER SUBSTANCES
Extracted: cimetidine

KEYWORDS
serum; whole milk; ranitidine is IS
REFERENCE
Oo, CY.; Kuhn, R.J.; Desai, N.; McNamara, RJ. Active transport of cimetidine into human milk.
Clin.Pharmacol.Ther., 1995, 58, 548-555

SAMPLE
Matrix: blood, tissue
Sample preparation: Blood. 25 |JLL Plasma + 100 JXL 75 JXM nizatidine + 100 |JLL 5 M
NQkQL -I 5 TXVLI <licKLororn.otKa.rvG, sKa.k.e for 10 miri^ c e n t r i f u g e a t 1650 g for 10 m i n
""Remove 4 mL oltne orgariicflayer arih e^HpTn^Vix\T);hTynesb^m&
room temperature, reconstitute the residue in 100 JJLL mobile phase, inject a 50 ^xL aliquot.
(Hemolyze 25 jxL whole blood with 200 |xL water then proceed as above.) Tissue. Homog-
enize brain tissue with 100 |xL 30 \xM nizatidine and 1 mL saline at 0 for 1 min, add
100 |JLL 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 |JLL mobile phase, cen-
trifuge at 10000 g, inject a 50 fxL aliquot.

HPLC VARIABLES
Column: 250 X 4 Senshu gel 7C18H (Senshu, Tokyo)
Mobile phase: MeCN: buffer 5:95. (Buffer was 5 mM NaH2PO4 containing 5 mM tetra-
methylammonium chloride.)
Column temperature: 30
Flow rate: 2
Injection volume: 50
Detector: UV 320

CHROMATOGRAM
Internal standard: nizatidine
Limit of detection: 1 |JLM (blood); 0.5 nmole/g (brain)

KEYWORDS
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: blood, urine
Sample preparation: Plasma. 250 fxL Plasma + 75 \xL 20 jxg/mL metoclopramide + 300
|xL 2 M NaOH, vortex for 30 s, add 5 mL dichloromethane, mix for 2 min, centrifuge at
10000 rpm for 15 min. Remove the organic layer and evaporate to dryness under nitrogen.
Reconstitute the residue in 150 |xL mobile phase, inject a 50 |xL aliquot. Urine. Dilute
100 |xL urine + 75 |xL 2 mg/mL metoclopramide to 10 mL with water, inject a 50 JLJLL
aliquot.

HPLCVARIABLES
Column: 250 X 4.6 Spherisorb S 5 ODS II
Mobile phase: MeCN: MeOH: buffer 60:30:5, pH adjusted to 3.8 with glacial acetic acid
(Buffer was 50 mM ammonium acetate containing 10 mM sodium octane sulfonate.)
Flow rate: 1.2
Injection volume: 50
Detector: UV 330

CHROMATOGRAM
Retention time: 5
Internal standard: metoclopramide (8)
Limit of detection: 20 ng/mL

OTHER SUBSTANCES
Simultaneous: acetaminophen, chlorodiazepam, chlorpromazine, desmethyldiazepam, di-
azepam, oxazepam, theobromine, theophylline

KEYWORDS
plasma

REFERENCE
Shiekh Salem, M.; Gharaibeh, A.M.; Alkaysi, H.N.; Badwan, A. High-performance liquid chromato-
graphic analysis of ranitidine in plasma and urine. J.Clin.Pharm.Ther., 1988, 13, 351-357

SAMPLE
Matrix: blood, urine
Sample preparation: Plasma. 2 mL Plasma + 200 |xL 5 M NaOH, vortex for a few seconds,
add 10 mL dichloromethane, vortex for 10 min, centrifuge at 1200 g for 10 min. Remove
the organic layer and evaporate it to dryness under nitrogen at 40. Reconstitute in 100
|xL water, inject a 20-50 JJLL aliquot. Urine. Dilute 1:50 with water, vortex for a few
seconds, centrifuge at 1200 g for 5 min, extract the supernatant as described above.

HPLCVARIABLES
Guard column: 50 X 4.6 Spherisorb CN
Column: 150 X 4.6 6 |xm Zorbax CN
Mobile phase: MeCN: 50 mM KH2PO4 15:85 containing 5 mM octanesulfonic acid
Flow rate: 2
Injection volume: 20-50
Detector: UV 318

CHROMATOGRAM
Retention time: 3.1
Internal standard: AH 20480 (4.2)
Limit of detection: 0.5 ng/mL
KEYWORDS
plasma
REFERENCE
Mullersman, G.; Derendorf, H. Rapid analysis of ranitidine in biological fluids and determination of its
erythrocyte partitioning. J.Chromatogr., 1986, 381, 385-391

SAMPLE
Matrix: formulations
Sample preparation: 100 |xL Injection + 50 fxL 200 |xg/mL caffeine in water + 850 JJLL
water, vortex briefly, inject a 50 \xh aliquot.
HPLCVARIABLES
Column: 250 X 4.6 Ultrasphere-ODS C18
Mobile phase: MeCN:buffer 8:92 (Buffer was 10 mM KH2PO4 adjusted to pH 5.0 with
phosphoric acid or NaOH.)
Flow rate: 2
Injection volume: 50
Detector: UV 262
CHROMATOGRAM
Retention time: 6
Internal standard: caffeine (3)
OTHER SUBSTANCES
Simultaneous: degradation products
KEYWORDS
stability-indicating; injections
REFERENCE
Hoyer, G.L.; LeDoux, J.; Nolan, RE., Jr. A sensitive stability indicating assay for the H2 blocker rani-
tidine. J.Liq.Chromatogr., 1995, 18, 1239-1249

SAMPLE
Matrix: formulations
Sample preparation: Dilute 1:4, inject a 20 |xL aliquot.
HPLCVARIABLES
Column: 250 X 4.6 5 |xm Adsorbosphere C18
Mobile phase: MeOH: 100 mM ammonium acetate 65:35
Flow rate: 1
Injection volume: 20
Detector: UV 322
CHROMATOGRAM
Retention time: 8.0
OTHER SUBSTANCES
Noninterfering: ondansetron, paclitaxel
KEYWORDS
injections; 5% dextrose; stability-indicating
REFERENCE
Burm, J.-R; Jhee, S.S.; Chin, A.; Moon, Y.S.K.; Jeong, E.; Nii, L.; Fox, J.L.; Gill, M.A. Stability of
paclitaxel with ondansetron hydrochloride or ranitidine hydrochloride during simulated Y-site ad-
ministration. Am. J.Hosp.Pharm., 1994, 51, 1201-1204

SAMPLE
Matrix: formulations
Sample preparation: Dilute 4:1 with saline, inject a 20 \xL aliquot.

HPLCVARIABLES
Column: 250 X 4.6 5 |xm Adsorbosphere
Mobile phase: MeOH: 100 mM ammonium acetate 65:35, pH adjusted to 4.0 with 1 M
NaOH
Flow rate: 1.2
Injection volume: 20
Detector: UV 322

CHROMATOGRAM
Retention time: 7.5

KEYWORDS
injections; saline; stability-indicating

REFERENCE
Choi, J.-S.; Burm, J.-R; Jhee, S.S.; Chin, A.; Ulrich, R.W.; Gill, M.A. Stability of piperacillin sodium-
tazobactam sodium and ranitidine hydrochloride in 0.9% sodium chloride injection during simulated
Y-site administration. Am.J.Hosp.Pharm., 1994, 51, 2273-2276

SAMPLE
Matrix: formulations
Sample preparation: Tablets. Grind tablets to a fine powder, weigh out a quantity equiv-
alent to about 150 mg ranitidine hydrochloride, add 50 mL MeOH: water 1:1, sonicate
for 10 min, dilute to 100 mL with MeOH: water 1:1, filter, dilute 5 mL filtrate to 100 mL
with MeOH: water 1:1, inject a 20 JULL aliquot. Injections, syrup. Measure out a volume
equivalent to about 75 mg ranitidine hydrochloride, dilute to 50 mL with MeOH.water
1:1, mix, dilute 5 mL to 100 mL with MeOH: water 1:1, inject a 20 JULL aliquot.

HPLCVARIABLES
Column: 150 X 4.6 5 |xm Microsorb-MV C18
Mobile phase: MeOH: 10 mM Na2HPO4 adjusted to pH 7.0 with phosphoric acid 50:50
Flow rate: 1
Injection volume: 20
Detector: UV 320

CHROMATOGRAM
Retention time: 3.44

KEYWORDS
tablets; injections; syrups

REFERENCE
Lau-Cam, CA.; Rahman, M.; Roos, R.W. Rapid reversed phase high performance liquid chromatographic
assay method for ranitidine hydrochloride in dosage forms. J.Liq.Chromatogr., 1994, 17, 1089-1104
SAMPLE
Matrix: formulations
Sample preparation: 100 [xL Solution + 1.9 mL MeOH: water 20:80, inject a 50 JXL
aliquot.

HPLCVARIABLES
Guard column: 5 jjtm Adsorbosphere C18
Column: 250 X 4.6 5 |xm Adsorbosphere C18
Mobile phase: MeOH: 100 mM ammonium acetate 65:35
Flow rate: 1
Injection volume: 50
Detector: UV 322

CHROMATOGRAM
Retention time: 6.5

KEYWORDS
stability-indicating; injections; saline

REFERENCE
Inagaki, K.; Gill, M.A.; Okamoto, M.P.; Takagi, J. Stability of ranitidine hydrochloride with aztreonam,
ceftazidime, or piperacillin sodium during simulated Y-site administration. Am. J.Hosp.Pharm., 1992,
49, 2769-2772

SAMPLE
Matrix: hepatocyte suspensions
Sample preparation: Add 2 volumes acetone to the hepatocyte suspension, centrifuge at
13000 g for 5 min. Remove the clear supernatant and evaporate it to dryness in a cen-
trifugal evaporator, reconstitute the residue in 1 mL MeOH, sonicate, centrifuge at 13000
g for 5 min, inject an aliquot.

HPLCVARIABLES
Column: 100 X 4.6 5 |xm ODS 1 (Jones Chromatography)
Mobile phase: MeCN: MeOH: 35 mM pH 7.0 phosphate buffer 5:46:49
Column temperature: 40
Detector: UV 320

CHROMATOGRAM
Retention time: 6.2
Limit of quantitation: 10 ng

OTHER SUBSTANCES
Extracted: metabolites

KEYWORDS
dog; rat

REFERENCE
Cross, D.M.; Bell, J.A.; Wilson, K. Kinetics of ranitidine metabolism in dog and rat isolated hepatocytes.
Xenobiotica, 1995, 25, 367-375

SAMPLE
Matrix: solutions
HPLCVARIABLES
Column: 250 X 4.6 10 jxm Partisil ODSl
Mobile phase: MeOH: 50 mM pH 3.0 phosphoric acid 10:90
Column temperature: 30
Flow rate: 1.5
Detector: Radioactivity

OTHER SUBSTANCES
Also analyzed: atenolol, cimetidine, hydrochlorothiazide
KEYWORDS
14
C labeled

REFERENCE
Collett, A.; Sims, E.; Walker, D.; He, Y-L.; Ayrton, J.; Rowland, M.; Warhurst, G. Comparison of HT29-
18-Ci and Caco-2 cell lines as models for studying intestinal paracellular drug absorption.
Pharm.Res., 1996, 13, 216-221

SAMPLE
Matrix: solutions

HPLCVARIABLES
Column: 150 X 4.6 12 |xm l-myristoyl-2-[(13-carboxyl)-tridecoyl]-sn-3-glycerophosphocho-
line 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' 0.96

OTHER SUBSTANCES
Also analyzed: acebutolol, alprenolol, antazoline, atenolol, betaxolol, bisoprolol, bopindolol,
bupranolol, carteolol, celiprolol, chloropyramine, chlorpheniramine, cicloprolol, cimeti-
dine, cinnarizine, cirazoline, clonidine, dilevalol, dimethindene, diphenhydramine, doxa-
zosin, esmolol, famotidine, isothipendyl, ketotifen, metiamide, metoprolol, moxonidine,
nadolol, naphazoline, nifenalol, nizatidine, oxprenolol, pheniramine, phentolamine, pin-
dolol, pizotyline (pizotifen), practolol, prazosin, promethazine, propranolol, pyrilamine
(mepyramine), ranitidine, roxatidine, sotalol, tiamenidine, timolol, tramazoline, tripelen-
namine, triprolidine, tymazoline, UK-14,304

REFERENCE
Kaliszan, R.; Nasal, A.; Turowski, M. Binding site for basic drugs on a r 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 ^m 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: 5.88 (A), 3.27 (B)

OTHER SUBSTANCES
Also analyzed: acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine,
albuterol, alprazolam, amitriptyline, amobarbital, amoxapine, antipyrine, atenolol, atro-
pine, azatadine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam,
bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine,
chlorcyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine,
chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimeti-
dine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchi-
cine, cyclizine, cyclobenzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal,
diltiazem, diphenhydramine, diphenidol, diphenoxylate, dipyridamole, disopyramide, do-
butamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine,
fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvox-
amine, furosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hy-
dralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydroxychloroquine, hydro-
xyzine, 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, na-
phazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, ox-
ycodone, 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, propran-
olol, protriptyline, quazepam, quinidine, quinine, racemethorphan, remoxipride, risperi-
done, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfin-
pyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline,
thiethylperazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide,
tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimepra-
zine, 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.Chromatogr.A, 1995, 692, 103-119

SAMPLE
Matrix: solutions

HPLCVARIABLES
Column: 250 X 4.6 Zorbax RX
Mobile phase: Gradient. A was 10 mL concentrated orthophosphoric acid and 7 mL trie-
thylamine in 1 L water. B was 10 mL concentrated orthophosphoric acid and 7 mL trie-
thylamine 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, aprobar-
bital, aspirin, atenolol, atropine, avermectin, barbital, benzocaine, benzoic acid, benzotro-
pine, benzphetamine, berberine, bibucaine, bromazepan, brompheniramine, buprenor-
phine, buspirone, butabarbital, butacaine, butethal, caffeine, carbamazepine, carbromal,
chloramphenieol, chlordiazepoxide, chloroquine, chlorothiazide, chloroxylenol, chlorphe-
nesin, 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, dex-
tromethorphan, dextropropoxyphene, diamorphine, diazepam, diclofenac, diethylpropion,
diethylstilbestrol, diflunisal, digitoxin, digoxin, diltiazem, diphenhydramine, diphpnoxy-
late, diprenorphine, dipyrone, disulfiram, dopamine, doxapram, doxepin, dronabinol,
ephedrine, epinephrine, epinine, estradiol, estriol, estrone, ethacrynic acid, ethosuximide,
etonitazene, etorphine, eugenol, famotidine, fenbendazole, fencamfamine, fenoprofen, fen-
proporex, fentanyl, flubendazole, flufenamic acid, flunitrazepam, 5-fluorouracil, fluo-
xymesterone, fluphenazine, furosemide, gentisic acid, gitoxigenin, glipizide, glunixin,
glutethimide, glybenclamide, guaiacol, halazepam, haloperidol, hydrochlorothiazide,
hydrocodone, hydrocortisone, hydromorphone, hydroxyquinoline, ibogaine, ibuprofen, im-
inostilbene, imipramine, indomethacin, isocarbostyril, isocarboxazid, isoniazid, isoproter-
enol, isoxsuprine, ivermectin, ketamine, ketoprofen, kynurenic acid, levorphanol, Ii-
docaine, lorazepam, lormetazepam, loxapine, mazindol, mebendazole, meclizine,
meclofenamic acid, medazepam, mefenamic acid, megestrol, mepacrine, meperidine, me-
phentermine, mephenytoin, mephesin, mephobarbital, mepivacaine, mescaline, mesori-
dazine, methadone, methamphetamine, methapyrilene, methaqualone, methazolamide,
methocarbamol, methoxamine, methsuximide, methyl salicylate, methyldopa, methyldo-
pamine, methylphenidate, methylprednisolone, methyltestosterone, methyprylon, meto-
prolol, mibolerone, morphine, nadolol, nalorphine, naloxone, naltrexone, naphazoline,
naproxen, nefopam, niacinamide, nicotine, nicotinic acid, nifedipine, niflumic acid, nitra-
zepam, nor epinephrine, nortriptyline, noscapine, nylidrin, oxazepam, oxycodone, oxymor-
phone, oxyphenbutazone, oxytetracycline, papaverine, pargyline, pemoline, pentazocine,
pentobarbital, persantine, phenacetin, phenazocine, phenazopyridine, phencyclidine,
phendimetrazine, phenelzine, pheniramine, phenobarbital, phenothiazine, phensuximide,
phentermine, phenylbutazone, phenylephrine, phenylpropanolamine, piperocaine, praze-
pam, prednisolone, primidone, probenecid, progesterone, propiomazine, propranolol, pro-
pylparaben, pseudoephedrine, puromycin, pyrilamine, pyrithyldione, quazepam, quinaldic
acid, quinidine, quinine, recinnamine, reserpine, resorcinol, saccharin, albuterol, salicy-
lamide, salicylic acid, scopolamine, scopoletin, secobarbital, strychnine, sulfacetamide, su-
fadiazine, sulfadimethoxine, sulfaethidole, sulfamerazine, sulfamethazine, sulfamethoxi-
zole, 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, tri-
amcinolone, tribenzylamine, trichloromethiazide, trifluoperazine, trihexyphenidyl, tri-
methoprim, tripelennamine, triprolidine, 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

SAMPLE
Matrix: solutions
Sample preparation: Prepare a 10 |xg/mL solution in MeOH, inject a 20 \xL aliquot.
HPLC VARIABLES
Column: 125 X 4.9 Spherisorb S5W silica
Mobile phase: MeOH containing 10 mM ammonium perchlorate and 1 mL/L 100 mM
NaOH in MeOH, pH 6.7
Flow rate: 2
Injection volume: 20
Detector: E, LeCarbone, V25 glassy carbon electrode, + 1.2 V

CHROMATOGRAM
Retention time: 3.1

OTHER SUBSTANCES
Also analyzed: acebutolol, acepromazine, acetophenazine, N-acetylprocainamide, albu-
terol, alprenolol, amethocaine, amiodarone, amitriptyline, antazoline, atenolol, azacy-
clonal, bamethane, benactyzine, benperidol, benzethidine, benzocaine, benzoctamine,
benzphetamine, benzquinamide, bromhexine, bromodiphenhydramine, bromperidol,
brompheniramine, brompromazine, buclizine, bufotenine, bupivacaine, buprenorphine,
butacaine, butethamate, chlorcyclizine, chlorpheniramine, chlorphenoxamine, chlorpren-
aline, chlorpromazine, chlorprothixene, cimetidine, cinchonidine, cinnarizine, clemastine,
clomipramine, clonidine, cocaine, cyclazocine, cyclizine, cyclopentamine, cyproheptadine,
deserpidine, desipramine, dextromoramide, dextropropoxyphene, dicyclomine, diethylcar-
bamazine, diethylpropion, diethylthiambutene, dihydroergotamine, dimethindene, di-
methothiazine, diphenhydramine, diphenoxylate, dipipanone, diprenorphine, dipyrida-
mole, disopyramide, dothiepin, doxapram, doxepin, doxylamine, droperidol, ephedrine,
ergocornine, ergocristine, ergocristinine, ergocryptine, ergometrine, ergosine, ergosinine,
ergotamine, ethopropazine, etorphine, etoxeridine, fenethazine, fenfluramine, fenoterol,
fentanyl, flavoxate, fluopromazine, flupenthixol, fluphenazine, flurazepam, haloperidol,
hydroxyzine, hyoscine, ibogaine, imipramine, indapamine, iprindole, isothipendyl, isox-
suprine, ketanserin, laudanosine, lidocaine, lofepramine, loxapine, maprotiline, mecamy-
lamine, meclophenoxate, meclozine, medazepam, mephentermine, mepivacaine, mep-
tazinol, mepyramine, mesoridazine, metaraminol, methadone, methamphetamine,
methapyrilene, methdilazene, methotrimeprazine, methoxamine, methoxyphenamine,
methoxypromazine, methylephedrine, methylergonovine, methysergide, metoclopramide,
metopimazine, metoprolol, mianserin, morazone, nadolol, nalorphine, naloxone, napha-
zoline, nicotine, nifedipine, nomifensine, nortriptyline, noscapine, orphenadrine, oxeladin,
oxprenolol, oxymetazolin, papaverine, pargyline, pecazine, penbutolol, pentazocine, pen-
thienate, pericyazine, perphenazine, phenadoxone, phenampromide, phenazocine, phen-
butrazate, phendimetrazine, phenelzine, phenglutarimide, phenindamine, pheniramine,
phenmetrazine, phenomorphan, phenoperidine, phenothiazine, phenoxybenzamine, phen-
tolamine, phenylephrine, phenyltoloxamine, physostigmine, piminodine, pimozide, pin-
dolol, pipamazine, pipazethate, piperacetazine, piperidolate, pipradol, pirenzepine, piri-
tramide, pizotifen, practolol, pramoxine, prazosin, prenylamine, prilocaine, primaquine,
proadifen, procainamide, procaine, prochlorperazine, procyclidine, proheptazine, prolin-
tane, promazine, promethazine, pronethalol, properidine, propiomazine, propranolol, pro-
thipendyl, protriptyline, proxymetacaine, pseudoephedrine, pyrimethamine, quinidine,
quinine, rescinnamine, sotalol, tacrine, terazosin, terbutaline, terfenadine, thenyldi-
amine, theophylline, thiethylperazine, thiopropazate, thioproperazine, thioridazine, thi-
othixene, thonzylamine, timolol, tocainide, tolpropamine, tolycaine, tranylcypromine, tra-
zodone, trifluoperazine, trifluperidol, trimeperidine, trimeprazine, trimethobenzamide,
trimethoprim, trimipramine, tripelennamine, triprolidine, tryptamine, verapamil,
xylometazoline

REFERENCE
Jane, L; McKinnon, A.; Flanagan, R. J. High-performance liquid chromatographic analysis of basic drugs
on silica columns using non-aqueous ionic eluents. II. Application of UV, fluorescence and electro-
chemical oxidation detection. J.Chromatogr., 1985, 323, 191-225

ANNOTATED BIBLIOGRAPHY
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simultaneous determination of two histamine H2-receptor antagonists, cimetidine and ranitidine, in
human plasma. J.Toxicol.Clin.Exp., 1988, 8, 387-394
Lant, M.S.; Martin, L.E.; Oxford, J. Qualitative and quantitative analysis of ranitidine and its metab-
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