OmeprazoleMolecular formula: C17H19N3O3S Molecular weight: 345.4 CAS Registry No.: 73590-58-6 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 D. omeprazole has been determined using this assay. (Buffer was MeCN: water 35:65 containing 1 mL/L n-octylamine and 5 mM N-acetohydroxamic acid.) HPLCVARIABLES Column: 150 or 250 X 4.5 Injection volume: 100 Detector: UV 285 CHROMATOGRAM Retention time: 7. centrifuge at 2000 g for 5 . 182-186 SAMPLE Matrix: blood Sample preparation: 1 mL Plasma + 100 JULL MeOH: 75 mM pH 9.6 Internal standard: omeprazole OTHER SUBSTANCES Extracted: lansoprazole KEYWORDS plasma.73) Limit of quantitation: 15 ng/mL OTHER SUBSTANCES Extracted: metabolites KEYWORDS plasma.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. Alexander. omeprazole is IS. 666.M.H. chiral. Enantioselective high-performance liquid chromatographic determination of omeprazole in human plasma. Granneman. pH adjusted to 7. R. 323328 SAMPLE Matrix: blood Sample preparation: 500 |xL Plasma + 150 |xL water + 5 mL diethyl ether: dichloromethane 70:30. Determination of lansoprazole and five metabolites in plasma by high-performance liquid chromatography. A.Chromatogr.Chromatogr..B..L. 668. 1995. 1995. 1995. Remove 4 mL of the organic layer and evaporate to dryness under reduced pressure at room temperature. 2078) REFERENCE Karol. 39.D. Sweden) (9. vortex for 5 min. J.lH-benzimidazole (Astra. M. SPE REFERENCE Cairns.5 with 85% phosphoric acid. Demetriades.B.R. refrigerate until injection. J. Hassle AB. reconstitute the residue in 500 |xL buffer.3 carbonate buffer 20:80 + 5 mL dichloromethane: MeCN 80:20. J. mix for 10 min. centrifuge at 6° at 300-850 g for 10 min.6-dimethyl. K.-Y. Rogers. Agents Chemother. protect from light. LOQ 10 ng/mL (Antimicrob. G.. Chiou. pH adjusted to 7.88 (+).27 (-) Internal standard: 2-([(4-methoxy-2-pyridinyl)methyl]sulfinyl)-4..CHROMATOGRAM Retention time: 13.0 with 85% phosphoric acid Column temperature: 40-43 Flow rate: 1 for 15 min then 2. J. 18. inject a 100 (xL aliquot. aceprometazine. demexiptiline. cyamemazine. debrisoquine. Y. K.6 5 jim Nucleosil 5C18 Mobile phase: MeCN: 20 mM pH 7. bisoprolol. Yamamoto. chlorophenacinone. carteolol. diazox- . clozapine. cytarabine. chlorpheniramine. bupivacaine. clorazepate. codeine. brompheniramine. HPLCVARIABLES Column: 250 X 4. 718-723 SAMPLE Matrix: blood Sample preparation: 2 mL Whole blood or plasma + 2 mL buffer + 5 mL chloroform: isopropanol: n-heptane 60:14:26.8 Injection volume: 50 Detector: UV 303 CHROMATOGRAM Retention time: 3. dextromoramide.min. chlorpropamide. atenolol. buprenorphine. ajmaline. aconitine. Comparative pharmacokinetic/pharmacodynamic study of proton pump inhibitors. caffeine. daunorubicin. chlorambucil. reconstitute the residue in 250 |xL mobile phase. inject a 50 |JLL aliquot of the supernatant. acetaminophen. clobazam.. omeprazole and lansoprazole in rats. Sugiura. dacarbazine. chlormezanone.) (At the end of each session wash the column with water for 1 h and MeOH for 1 h. dextropropoxyphene. dextromethorphan. T. colchicine. benzocaine.) Column temperature: 30 Flow rate: 0. Iga. benazepril. M. carbinoxamine. clomipramine. benperidol. shake gently horizontally for 10 min. desipramine. betaxolol. Remove the lower organic layer and evaporate it to dryness under vacuum at 45°. Drug Metab.. buspirone. Sawada. cibenzoline. carpipramine. inject a 100 |JLL aliquot. chlorpromazine. albuterol. cocaine..68 g/L (10 mM (sic)) KH2PO4 adjusted to pH 2. 1995. amitriptyline. astemizole. centrifuge at 2800 g for 5 min. celiprolol. bepridil. alimemazine. clonidine. reconstitute the residue in 100 JULL mobile phase. clemastine. M. cicletanine. diazepam. re-equilibrate for 30 min. alminoprofen.) HPLCVARIABLES Column: 300 X 3. cetirizine. amoxapine. amisulpride. Remove 4 mL of the organic layer and evaporate it to dryness under a stream of nitrogen. ehloroquine. plasma.23.6 with concentrated orthophosphoric acid. cyproheptadine. aspirin. pharmacokinetics REFERENCE Katashima..72 Limit of detection: <120 ng/mL OTHER SUBSTANCES Extracted: acenocoumarol.Dispos. clonazepam. alprenolol. amodiaquine. centrifuge at 2800 g for 10 min. acepromazine. alprazolam.5 with 25% ammonia solution. cyclizine. cycloguanil.9 4 |xm NovaPack C18 Mobile phase: MeOH:THF:buffer 65:5:30 (Buffer was 0. (Buffer was saturated ammonium chloride solution 25% diluted with water.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. adjusted to pH 9. benzoylecgonine.. bumadizone. chlordiazepoxide. alpidem. terfenadine. sotalol.2 Internal standard: 5-methyl-2-[[(4-methoxy-3. moclobemide.. carbamazepine. nicardipine. glipizide. fenfluramine. lorazepam.5-dimethyl-2-pyridinyl)methyl]sulfinyl]-lHbenzimidazole (H 168/24) (11. trifluperidol. naloxone. sulindac. G. U. penbutolol. iproniazid. HPLCVARIABLES Column: 120 mm long 5 |xm Hypersil ODS Mobile phase: MeOH: water: triethylamine 55:44:1. nimodipine. midazolam. tropatenine. nifedipine. propafenone... fluphenazine. proguanil. trimipramine. flecainide. suriclone. inject an aliquot. lidocaine. Klotz. phenobarbital. flunitrazepam. zopiclone. metoprolol. dihydralazine. droperidol. prazepam. floctafenine. zorubicine Interfering: acebutolol. imipramine. tiaprofenic acid. triazolam. Systematic toxicological analysis using HPLC/DAD. tenoxicam. pimozide. pentazocine. disopyramide. protriptyline. zolpidem. yohimbine. naltrexone. ketamine. lidoflazine. sultopride. tetrazepam. doxepin. nadolol. mefenidramine. pyrimethamine. diltiazem. ephedrine. procainamide. vindesine.Pharmacol. histapyrrodine. extract. loxapine. diphenhydramine. mianserine. glibenclamide. viloxazine. fluoxetine. medifoxamine. penfluridol. nizatidine. ritodrine. terbutaline. phenylbutazone. warfarin. quinine.. lisinopril. moperone. labetalol. promethazine.Forensic Sci. estazolam. doxylamine. oxazepam. melphalan. tioclomarol. ibuprofen. indomethacin. 254-262 SAMPLE Matrix: blood Sample preparation: 1 mL Plasma + 500 ng IS + 6 mL dichloromethane. propranolol. meperidine. medazepam. nitrendipine. plasma REFERENCE Tracqui. dissolve the residue in 100 |xL mobile phase. s^cobarbital. fentiazac. toloxatone. nalbuphine. thiopental. temazepam. verapamil. morphine. mexiletine. methaqualone. mephentermine. methotrexate. ketoprofen. Kintz. minoxidil. nortriptyline.8 Detector: UV 302 CHROMATOGRAM Retention time: 7. mepivacaine. trifluoperazine. reserpine. ticlopidine. fenoprofen. P. ramipril. methocarbamol. sulfinpyrazole. quinupramine. flurbiprofen. loprazolam. mefenamic acid. opipramol. vincristine. tolbutamide.Ther. maprotiline. tofisopam. phenol. tetracaine. dosulepine. tianeptine. glibornuride. nalorphine.. haloperidol. P. timolol.. ranitidine. strychnine KEYWORDS whole blood. Clin. triprolidine. methadone. Walker. diclofenac. A. S. fluvoxamine. prilocaine.ide. nitrazepam. pipamperone. quinidine. 55. centrifuge. dipyridamole. mefloquine. hydroxyzine. nomifensine. Mangin. thioridazine. niflumic acid. Omeprazole-induced increase in the absorption of bismuth from tripotassium dicitrato bismuthate. loratadine. metoclopramide. trazodone. mephenesin. 1995. bromazepam. piroxicam. J. phencyclidine. sulpride. tiapride. 40. prazosin. nialamide. vinblastine. thioproperazine. naproxen. metformin. glutethimide. oxprenolol. 486-491 . flumazenil. pH 7 Flow rate: 0. metipranolol. hydroxychloroquine. pindolol. etodolac. metapramine.0) Limit of quantitation: 10 ng/mL KEYWORDS plasma REFERENCE Treiber. procarbazine. loperamide. 1994. levomepromazine. Remove organic layer and evaporate it. 309. K. Add 20 |xL plasma + 40 ng nitrazepam to SPE cartridge. elute with 250 |xL MeOH.ScL. mix.. J.Chromatogr. 83. inject a 60 |xL aliquot of the eluate.5 5 |xm LiChrosorb Si 60 Mobile phase: Dichloromethane: MeOH containing 5% concentrated ammonium hydroxide 96. wash with 2 mL water. K.. Gomita. Determination of omeprazole and metabolites in plasma and urine by liquid chromatography J. 1984. 1994. HPLCVARIABLES Column: 150 X 4.. 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. Eto. shake for 10 min..Pharm.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. K. normal phase REFERENCE Lagerstrom. Oishi..5:3. Furuno. add 1 mL dichloromethane. rat. R. R-O. Y.1) 20:80. centrifuge twice at 2500 g for 10 min.5 Flow rate: 1. HPLCVARIABLES Column: 125 X 4 4 |xm LiChro CART C18 Mobile phase: MeCN: 20 mM pH 7. inject a 150 fxL aliquot of the organic layer. First-pass metabolism of omeprazole in rats. B.-A. pharmacokinetics REFERENCE Watanabe. Persson.SAMPLE Matrix: blood Sample preparation: Condition a Bond Elut C18 SPE cartridge with 2 mL MeOH and 2 mL water.6-dimethyl-2-[[(4-methoxy-2-pyridinyl)methyl]sulfinyl]-lH-benzimidazole (H153/52) (5..5 Injection volume: 150 Detector: UV 302 CHROMATOGRAM Retention time: 4 Internal standard: 4. 347-356 .3 carbonate buffer (I = 0.5) Limit of detection: 20 nM (plasma) OTHER SUBSTANCES Extracted: metabolites KEYWORDS plasma. SPE. pharmacokinetics REFERENCE Kobayashi. vortex for 10 min. reconstitute the residue in 500 |xL MeCN :pH 7. 1 mL Plasma + 100 |xL 100 jxg/mL phenacetin in MeOH + 5 mL dichloromethane H. D.6 5 |im Capcell Pak C18 SG 120 (Shiseido) Mobile phase: MeCN: 50 mM pH 8.Chromatogr.0 phosphate buffer.5 M pH 8.. 579. HPLCVARIABLES Column: 250 X 4.. mix. inject a 10-30 IxL aliquot.6) Limit of quantitation: 10 ng/mL OTHER SUBSTANCES Extracted: metabolites Noninterfering: cimetidine.. Y. T. Chiba. ranitidine. urine Sample preparation: Plasma. urine Sample preparation: 1 mL Plasma or urine + 100 JJLL 1 M NaH2PO4 + 100 \xL 50-100 |xg/mL IS in MeOH :pH 9.5 phosphate buffer (1=0. 299-305 SAMPLE Matrix: blood. Kato. famotidine KEYWORDS plasma.5 phosphate buffer (1=0. K. add 10 mL dichloromethane.6 Spheri-5 RP-8 Column: 150 X 4.5 M pH 8. 1 mL Urine + 100 |xL 200 |JLg/mL phenacetin in MeOH + 5 mL dichloromethane + 250 mg NaCl + 500 |JLL 0. centrifuge at 1610 g for 30 min.3 carbonate buffer (I = 0. J.. HPLC VARIABLES Guard column: 30 X 4. Remove 8 mL of the organic layer and evaporate it to dryness under a stream of nitrogen at room temperature. filter (0. Sohn. Remove the organic phase and evaporate it under vacuum at 40°. centrifuge at 1610 g for 30 min. inject a 150 |xL aliquot. centrifuge at 2500 g for 10 min.45 fim). vortex for 10 min.05) 30:70 Flow rate: 1 Injection volume: 150 Detector: UV 302 CHROMATOGRAM Retention time: 7.250 mg NaCl + 500 JJLL 0. shake for 10 min.5 5 |xm Polygosil C18 (Macherey-Nagel) Mobile phase: MeCN :pH 7.8 Injection volume: 10-30 Detector: UV 302 CHROMATOGRAM Retention time: 16. inject a 30 JJLL aliquot. Urine. reconstitute the residue with 200 |xL mobile phase.SAMPLE Matrix: blood.05). K. 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.5 . Remove the organic phase and evaporate it under vacuum at 40°.. 1992.8 Internal standard: phenacetin (13.1) 20:80.0 phosphate buffer. Ishizaki. reconstitute the residue with 300 \xL mobile phase.5 phosphate buffer 25:75 Flow rate: 0.-R. centrifuge at 1000 g for 5 min.-A. Veronese.6 Chiralpak AD Mobile phase: Hexane: EtOH 80:20 Column temperature: 35 Flow rate: 1 . Persson.E. 347-356 SAMPLE Matrix: microsomal incubations Sample preparation: 1 mL Incubation mixture + 2 mL dichloromethane:butanol 99:1. R-O. J. Birkett. inject a 10-20 (xL aliquot. vortex for 1 min..3) OTHER SUBSTANCES Extracted: metabolites KEYWORDS normal phase REFERENCE Andersson.5-dimethyl-2-p3rridinyl)methyl]sulfinyl]-lHbenzimidazole (H168/24) (10) Limit of quantitation: 25 nM (plasma). ranitidine KEYWORDS plasma REFERENCE Lagerstrom.J. reconstitute in 150 |xL mobile phase. B. T.. 50 nM (urine) OTHER SUBSTANCES Extracted: metabolites Noninterfering: cimetidine.O.5 Injection volume: 50 Detector: UV 302 CHROMATOGRAM Retention time: 2. 1993. M.Chromatogr..6-Dimethyl-2-[[(4-methoxy-2-pyridinyl)methyl]sulfinyl]-lH-benzimidazole (3.Chromatogr.. add 100 fxL 1 M NaH2PO4 + IS. 1984.. 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 Internal standard: 4. D. J. High-performance liquid chromatographic assay for human liver microsomal omeprazole metabolism. Lagerstrom. L. Remove 1. 309. HPLCVARIABLES Column: 250 X 4. Miners.. cool on ice. inject a 50 |xL aliquot..5 mL of the organic phase and evaporate it to dryness under nitrogen.. 619. Determination of omeprazole and metabolites in plasma and urine by liquid chromatography. 291-297 SAMPLE Matrix: solutions Sample preparation: Prepare a solution in EtOH.Internal standard: 5-methyl-2-[[(4-methoxy-3. Weidolf. R-O. J. Isaksson.Pharm. Comparison of the kinetic disposition and metabolism of E3810.... K. K.M. M. 586.Injection volume: 10-20 Detector: UV 302 CHROMATOGRAM Retention time: k' 4. Tomono. R. Yamato. 1994. J.Pharmacol. S.A. 12. K. 1991. 1995. 269-273 • • • ANNOTATED BIBLIOGRAPHY Yasuda. Kuroiwa. 305-319 Amantea.. P. E.J.. Lorentzon.86 (of first (—) enantiomer) OTHER SUBSTANCES Simultaneous: lansoprazole. H. a new proton pump inhibitor.Chromatogr. Tivert.. Chiba.... pantoprazole. Kobayashi..Chromatogr. 426. Collijn.. J. The effect of the enantiomers of omeprazole on gastric glands. K. J. P. a = 1.. 1990.A. Rosen. 1988. J. W. 311-319 .D. Peak distortion in the column liquid chromatographic determination of omeprazole dissolved in borax buffer. Clin.Ther. P.AnaL. Stereoselective effects in the separation of enantiomers of omeprazole and other substituted benzimidazoles on different chiral stationary phases. R-O.Chromatogr. J.. Ishizaki. Development and preliminary application of a high-performance liquid chromatographic assay for omeprazole metabolism in human liver microsomes. 143-154 [LOQ 5 ng/mL. 278. Horai. 58. timoprazole KEYWORDS chiral...81 REFERENCE Balmer.-A. C.J. and omeprazole in relation to S-mephenytoin 4'-hydroxylation status.Chromatogr. 839-844 Arvidsson.. T.. Improved procedure for quantitation of omeprazole and metabolites using reversed-phase high-performance liquid chromatography. Prichard. M. K. Y. Narang. Simultaneous high-performance liquid chromatographic analysis of omeprazole and its sulphone and sulphide metabolites in human plasma and urine. Lagerstrom. B. Y. Nakai. Smallwood... Manabe.... PK.. Persson. Chiba.W. A. 1983. Tani.Biomed. Ishizaki. pharmacokinetics] Kobayashi. Lindberg. N.. Louis. R. P. G. Resolution of the enantiomers of omeprazole and some of its analogues by liquid chromatography on a trisphenylcarbamoylcellulose-based stationary phase. 660.Chromatogr. Y. K.. 216-222 Mihaly. 1994. Yeomans.A. J. T. T. L. 271-276 Erlandsson.. 532.