Omeprazole: Sample
Omeprazole: Sample
Omeprazole: Sample
SAMPLE
Matrix: blood
Sample preparation: 1 mL Serum + 1 \Lg IS + 5 mL dichloromethane, extract. Remove
the organic layer and evaporate it to dryness under a stream of nitrogen at room temperature, reconstitute the residue in mobile phase, inject a 100 JJLL aliquot.
HPLCVARIABLES
Column: 300 X 3.9 p,Bondapak C18
Mobile phase: MeOH: water 50:50 containing 1% triethylamine, pH adjusted to 7.4 with
phosphoric acid
Flow rate: 2
Injection volume: 100
Detector: UV 302
CHROMATOGRAM
Retention time: 5.3
Internal standard: 5-methyl-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-IHbenzimidazole (H168/24) (8.4)
Limit of quantitation: 50 ng
OTHER SUBSTANCES
Extracted: metabolites
KEYWORDS
serum
REFERENCE
Balian, J.D.; Sukhova, N.; Harris, J.W.; Hewett, J.; Pickle, L.; Goldstein, J.A.; Woosley, R.L.; Flockhart,
D.A. The hydroxylation of omeprazole correlates with S-mephenytoin metabolism: A population
study. Clin.Pharmacol.Ther., 1995, 57, 662-669
SAMPLE
Matrix: blood
Sample preparation: Condition a 100 mg C2 SPE cartridge (Varian) with 1 mL MeOH
and 1 mL water. 1 mL Plasma + 50 |xL 5 |jig/mL IS, add to SPE cartridge, apply a vacuum
so the sample moves through at 0.5 mL/min, wash with 1 mL water, dry under vacuum
for 10 min, elute with two 1 mL portions of MeCN (do not allow to run dry). Evaporate
the eluate to dryness under a stream of nitrogen at room temperature, reconstitute the
residue in 50 |JLL MeOH, vortex for 2 min, add 200 |xL pH 9.3 carbonate buffer, inject a
100-190 fxL aliquot.
HPLCVARIABLES
Column: 150 X 4 5 fjim Resolvosil BSA-7 bovine serum albumin (Macherey-Nagel)
Mobile phase: n-Propanol: 50 mM pH 7.0 ammonium phosphate buffer 0.75:99.25 (n-Propanol concentration should be optimized for each column over the range 0.05-1%.)
Flow rate: 1.5
Injection volume: 100-190
Detector: UV 302
CHROMATOGRAM
Retention time: 13.88 (+), 18.27 (-)
Internal standard: 2-([(4-methoxy-2-pyridinyl)methyl]sulfinyl)-4,6-dimethyl- lH-benzimidazole (Astra, Hassle AB, Sweden) (9.73)
Limit of quantitation: 15 ng/mL
OTHER SUBSTANCES
Extracted: metabolites
KEYWORDS
plasma; chiral; protect from light; SPE
REFERENCE
Cairns, A.M.; Chiou, R.H.-Y; Rogers, J.D.; Demetriades, J.L. Enantioselective high-performance liquid
chromatographic determination of omeprazole in human plasma. J.Chromatogr.B, 1995, 666, 323328
SAMPLE
Matrix: blood
Sample preparation: 500 |xL Plasma + 150 |xL water + 5 mL diethyl ether: dichloromethane 70:30, vortex for 5 min, centrifuge at 6 at 300-850 g for 10 min. Remove 4 mL of
the organic layer and evaporate to dryness under reduced pressure at room temperature,
reconstitute the residue in 500 |xL buffer, refrigerate until injection, inject a 100 (xL aliquot. (Buffer was MeCN: water 35:65 containing 1 mL/L n-octylamine and 5 mM N-acetohydroxamic acid, pH adjusted to 7.5 with 85% phosphoric acid.)
HPLCVARIABLES
Column: 150 or 250 X 4.6 5 jim Hi-Chrom Reversible octadecylsilane (Regis)
Mobile phase: MeCN: water 35:65 containing 1 mL/L n-octylamine and 5 mM N-acetohydroxamic acid, pH adjusted to 7.0 with 85% phosphoric acid
Column temperature: 40-43
Flow rate: 1 for 15 min then 2.5
Injection volume: 100
Detector: UV 285
CHROMATOGRAM
Retention time: 7.6
Internal standard: omeprazole
OTHER SUBSTANCES
Extracted: lansoprazole
KEYWORDS
plasma; omeprazole is IS; omeprazole has been determined using this assay, LOQ 10 ng/mL
(Antimicrob. Agents Chemother. 1995, 39, 2078)
REFERENCE
Karol, M.D.; Granneman, G.R.; Alexander, K. Determination of lansoprazole and five metabolites in
plasma by high-performance liquid chromatography. J.Chromatogr.B, 1995, 668, 182-186
SAMPLE
Matrix: blood
Sample preparation: 1 mL Plasma + 100 JULL MeOH: 75 mM pH 9.3 carbonate buffer
20:80 + 5 mL dichloromethane: MeCN 80:20, mix for 10 min, centrifuge at 2000 g for 5
min. Remove 4 mL of the organic layer and evaporate it to dryness under a stream of
nitrogen, reconstitute the residue in 250 |xL mobile phase, inject a 100 |JLL aliquot.
HPLCVARIABLES
Column: 250 X 4.6 5 jim Nucleosil 5C18
Mobile phase: MeCN: 20 mM pH 7.5 phosphate buffer 37:63
Column temperature: 40
Flow rate: 1
Injection volume: 100
Detector: UV 302
CHROMATOGRAM
Limit of quantitation: 5 ng/mL
KEYWORDS
rat; plasma; pharmacokinetics
REFERENCE
Katashima, M.; Yamamoto, K.; Sugiura, M.; Sawada, Y.; Iga, T. Comparative pharmacokinetic/pharmacodynamic study of proton pump inhibitors, omeprazole and lansoprazole in rats. Drug
Metab.Dispos., 1995,23, 718-723
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 JULL mobile phase, centrifuge at 2800 g for 5 min,
inject a 50 |JLL 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 |xm 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 303
CHROMATOGRAM
Retention time: 3.72
Limit of detection: <120 ng/mL
OTHER SUBSTANCES
Extracted: acenocoumarol, acepromazine, aceprometazine, acetaminophen, aconitine,
ajmaline, albuterol, alimemazine, alminoprofen, alpidem, alprazolam, alprenolol, amisulpride, amitriptyline, amodiaquine, amoxapine, aspirin, astemizole, atenolol, benazepril,
benperidol, benzocaine, benzoylecgonine, bepridil, betaxolol, bisoprolol, brompheniramine,
bumadizone, bupivacaine, buprenorphine, buspirone, caffeine, carbinoxamine, carpipramine, carteolol, celiprolol, cetirizine, chlorambucil, chlordiazepoxide, chlormezanone,
chlorophenacinone, ehloroquine, chlorpheniramine, chlorpromazine, chlorpropamide,
cibenzoline, cicletanine, clemastine, clobazam, clomipramine, clonazepam, clonidine,
clorazepate, clozapine, cocaine, codeine, colchicine, cyamemazine, cyclizine, cycloguanil,
cyproheptadine, cytarabine, dacarbazine, daunorubicin, debrisoquine, demexiptiline, desipramine, dextromethorphan, dextromoramide, dextropropoxyphene, diazepam, diazox-
ide, diclofenac, 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,
lisinopril, loperamide, loprazolam, loratadine, lorazepam, loxapine, maprotiline, medazepam, medifoxamine, mefenamic acid, mefenidramine, mefloquine, melphalan, meperidine, mephenesin, mephentermine, mepivacaine, metapramine, metformin, methadone,
methaqualone, methocarbamol, methotrexate, metipranolol, metoclopramide, metoprolol,
mexiletine, mianserine, midazolam, minoxidil, moclobemide, moperone, morphine, nalorphine, naloxone, naltrexone, naproxen, nialamide, nicardipine, nifedipine, niflumic acid,
nimodipine, nitrazepam, nitrendipine, nizatidine, nomifensine, nortriptyline, opipramol,
oxazepam, oxprenolol, penbutolol, penfluridol, pentazocine, phencyclidine, phenobarbital,
phenol, phenylbutazone, pimozide, pindolol, pipamperone, piroxicam, prazepam, prazosin,
prilocaine, proguanil, promethazine, propafenone, propranolol, protriptyline, pyrimethamine, quinidine, quinine, quinupramine, ramipril, ranitidine, reserpine, ritodrine, s^cobarbital, sotalol, sulfinpyrazole, sulindac, sulpride, sultopride, 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: acebutolol, bromazepam, carbamazepine, dihydralazine, nadolol, nalbuphine,
procainamide, procarbazine, strychnine
KEYWORDS
whole blood; plasma
REFERENCE
Tracqui, A.; Kintz, P.; Mangin, P. Systematic toxicological analysis using HPLC/DAD. J.Forensic Sci.,
1995, 40, 254-262
SAMPLE
Matrix: blood
Sample preparation: 1 mL Plasma + 500 ng IS + 6 mL dichloromethane, extract, centrifuge. Remove organic layer and evaporate it, dissolve the residue in 100 |xL mobile
phase, inject an aliquot.
HPLCVARIABLES
Column: 120 mm long 5 |xm Hypersil ODS
Mobile phase: MeOH: water: triethylamine 55:44:1, pH 7
Flow rate: 0.8
Detector: UV 302
CHROMATOGRAM
Retention time: 7.2
Internal standard: 5-methyl-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-lHbenzimidazole (H 168/24) (11.0)
Limit of quantitation: 10 ng/mL
KEYWORDS
plasma
REFERENCE
Treiber, G.; Walker, S.; Klotz, U. Omeprazole-induced increase in the absorption of bismuth from tripotassium dicitrato bismuthate. Clin.Pharmacol.Ther., 1994, 55, 486-491
SAMPLE
Matrix: blood
Sample preparation: Condition a Bond Elut C18 SPE cartridge with 2 mL MeOH and 2
mL water. Add 20 |xL plasma + 40 ng nitrazepam to SPE cartridge, wash with 2 mL
water, elute with 250 |xL MeOH, inject a 60 |xL aliquot of the eluate.
HPLCVARIABLES
Column: 125 X 4 4 |xm LiChro CART C18
Mobile phase: MeCN: 20 mM pH 7.4 Na2HPO4 35:65
Flow rate: 1
Injection volume: 60
Detector: UV 310
CHROMATOGRAM
Internal standard: nitrazepam
Limit of detection: 25 ng/mL
KEYWORDS
plasma; rat; SPE; pharmacokinetics
REFERENCE
Watanabe, K.; Furuno, K.; Eto, K.; Oishi, R.; Gomita, Y. First-pass metabolism of omeprazole in rats.
J.Pharm.ScL, 1994, 83, 1131-1134
SAMPLE
Matrix: blood
Sample preparation: 1 mL Plasma + 100 \xL 1 M NaH2PO4 + 100 JULL 50-100 |xg/mL IS
in MeOH :pH 9.3 carbonate buffer (I = 0.1) 20:80, mix, add 1 mL dichloromethane, shake
for 10 min, centrifuge twice at 2500 g for 10 min, inject a 150 fxL aliquot of the organic
layer.
HPLCVARIABLES
Column: 150 X 4.5 5 |xm LiChrosorb Si 60
Mobile phase: Dichloromethane: MeOH containing 5% concentrated ammonium hydroxide
96.5:3.5
Flow rate: 1.5
Injection volume: 150
Detector: UV 302
CHROMATOGRAM
Retention time: 4
Internal standard: 4,6-dimethyl-2-[[(4-methoxy-2-pyridinyl)methyl]sulfinyl]-lH-benzimidazole (H153/52) (5.5)
Limit of detection: 20 nM (plasma)
OTHER SUBSTANCES
Extracted: metabolites
KEYWORDS
plasma; normal phase
REFERENCE
Lagerstrom, R-O.; Persson, B.-A. Determination of omeprazole and metabolites in plasma and urine by
liquid chromatography J.Chromatogr., 1984, 309, 347-356
SAMPLE
plasma; pharmacokinetics
REFERENCE
Kobayashi, K.; Chiba, K.; Sohn, D.-R.; Kato, Y.; Ishizaki, T. Simultaneous determination of omeprazole
and its metabolites in plasma and urine by reversed-phase high-performance liquid chromatography
with an alkaline-resistant polymer-coated C18 column. J.Chromatogr., 1992, 579, 299-305
SAMPLE
SAMPLE
Matrix: microsomal incubations
Sample preparation: 1 mL Incubation mixture + 2 mL dichloromethane:butanol 99:1,
cool on ice, add 100 fxL 1 M NaH2PO4 + IS, vortex for 1 min, centrifuge at 1000 g for 5
min. Remove 1.5 mL of the organic phase and evaporate it to dryness under nitrogen,
reconstitute in 150 |xL mobile phase, inject a 50 |xL aliquot.
HPLCVARIABLES
Guard column: 15 X 3 7 jxm Brownlee Aquapore silica
Column: 125 X 4 4 |xm Superspher SI-60
Mobile phase: Dichloromethane:5% ammonium hydroxide in MeOH:isopropanol 191:8:1
Flow rate: 1.5
Injection volume: 50
Detector: UV 302
CHROMATOGRAM
Retention time: 2.5
Internal standard: 4,6-Dimethyl-2-[[(4-methoxy-2-pyridinyl)methyl]sulfinyl]-lH-benzimidazole (3.3)
OTHER SUBSTANCES
Extracted: metabolites
KEYWORDS
normal phase
REFERENCE
Andersson, T.; Lagerstrom, R-O.; Miners, J.O.; Veronese, M.E.; Weidolf, L.; Birkett, D.J. High-performance liquid chromatographic assay for human liver microsomal omeprazole metabolism.
J.Chromatogr., 1993, 619, 291-297
SAMPLE
Matrix: solutions
Sample preparation: Prepare a solution in EtOH, inject a 10-20 (xL aliquot.
HPLCVARIABLES
Column: 250 X 4.6 Chiralpak AD
Mobile phase: Hexane: EtOH 80:20
Column temperature: 35
Flow rate: 1
chiral; a = 1.81
REFERENCE
Balmer, K.; Persson, B.-A.; Lagerstrom, R-O. Stereoselective effects in the separation of enantiomers of
omeprazole and other substituted benzimidazoles on different chiral stationary phases.
J.Chromatogr.A, 1994, 660, 269-273
ANNOTATED BIBLIOGRAPHY
Yasuda, S.; Horai, Y; Tomono, Y; Nakai, H.; Yamato, C; Manabe, K.; Kobayashi, K.; Chiba, K.; Ishizaki,
T. Comparison of the kinetic disposition and metabolism of E3810, a new proton pump inhibitor, and
omeprazole in relation to S-mephenytoin 4'-hydroxylation status. Clin.Pharmacol.Ther., 1995, 58,
143-154 [LOQ 5 ng/mL; pharmacokinetics]
Kobayashi, K.; Chiba, K.; Tani, M.; Kuroiwa, Y; Ishizaki, T. Development and preliminary application
of a high-performance liquid chromatographic assay for omeprazole metabolism in human liver microsomes. J.Pharm.Biomed.AnaL, 1994, 12, 839-844
Arvidsson, T.; Collijn, E.; Tivert, A.M.; Rosen, L. Peak distortion in the column liquid chromatographic
determination of omeprazole dissolved in borax buffer. J.Chromatogr., 1991, 586, 271-276
Erlandsson, P.; Isaksson, R.; Lorentzon, P.; Lindberg, P. Resolution of the enantiomers of omeprazole
and some of its analogues by liquid chromatography on a trisphenylcarbamoylcellulose-based stationary phase. The effect of the enantiomers of omeprazole on gastric glands. J.Chromatogr., 1990,
532, 305-319
Amantea, M.A.; Narang, PK. Improved procedure for quantitation of omeprazole and metabolites using
reversed-phase high-performance liquid chromatography. J.Chromatogr., 1988, 426, 216-222
Mihaly, G.W.; Prichard, P.J.; Smallwood, R.A.; Yeomans, N.D.; Louis, W.J. Simultaneous high-performance liquid chromatographic analysis of omeprazole and its sulphone and sulphide metabolites in
human plasma and urine. J.Chromatogr., 1983, 278, 311-319