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Molecular formula: C21H31N3O5 Molecular weight: 405.5 CAS Registry No.: 76547-98-3 (anhydrous), 83915-83-7 (dihydrate)

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 pX 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 |jim 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 259 CHROMATOGRAM Retention time: 3.50 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, astemizole, atenolol, benazepril, benperidol, benzoylecgonine, bepridil, betaxolol, bisoprolol, bromazepam, brompheniramine, bumadizone, bupivacaine, buprenorphine, buspirone, caffeine, carbamazepine, carbinoxamine, carpipramine, celiprolol, cetirizine, chlorambucil, chlordiazepoxide, 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, 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, phenylbutazone, pimozide, pindolol, pipamperone, piroxicam, prazepam, prazosin, prilocaine, procainamide, procarbazine, pro-

guanil, 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, aspirin, benzocaine, carteolol, chlormezanone, codeine, mephenesin, metformin, nalorphine, naloxone, naltrexone, nizatidine, phenol, ritodrine, sotalol, sultopride 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: solutions HPLCVARIABLES Column: 250 X 4.6 Spherisorb 5 ODS-2 Mobile phase: n-Propanol:buffer 5:95 (Buffer was pH 3.0 phosphate buffer containing 0.4% triethylamine.) Flow rate: 1 Detector: UV 240 CHROMATOGRAM Retention time: 8.2 REFERENCE
Barbato, R; Morrica, P.; Quaglia, F. Analysis of ACE inhibitor drugs by high performance liquid chromatography Farmaco, 1994, 49, 457-460

SAMPLE Matrix: solutions HPLCVARIABLES Column: 300 X 3.9 ixBondapak phenyl Mobile phase: MeOH: water: 85% phosphoric acid 60:40:0.05 Column temperature: 30-40 Detector: UV 215-220 OTHER SUBSTANCES Also analyzed: enalapril REFERENCE
Ranadive, S.A.; Chen, A.X.; Serajuddin, A.T. Relative lipophilicities and structural-pharmacological considerations of various angiotensin-converting enzyme (ACE) inhibitors. Pharm.Res., 1992, 9, 14801486

SAMPLE Matrix: urine

Sample preparation: Condition a Sep-Pak C18 SPE cartridge with 10 mL MeOH, 10 mL water, and 20 mL 100 mM HCl. 1 mL Urine + 80 |xL 8 fxg/mL enalaprilat + 10 |JLL 6 M nitric acid, vortex for 30 s, add to the SPE cartridge, wash with 20 mL 100 mM HCl, elute with 3 mL MeCN: water 10:90, elute with 6 mL water. Combine the eluates and evaporate the MeCN under a stream of air at 65, add 25 |xL 6 M nitric acid, add this solution to the SPE cartridge, wash with 10 mL chloroform, elute with 6 mL MeOH. Evaporate the eluate to dryness under a stream of air at 65, wash the residue with 1 mL MeCN, reconstitute with 500 JULL MeOH: chloroform 10:90, vortex for 30 s. Put this solution in an another tube, evaporate to dryness, reconstitute with 100 JJLL mobile phase, inject a 10 (JLL aliquot. HPLC VARIABLES Column: 300 X 3.9 10 \xm jxBondapak C18 Mobile phase: MeCN: MeOH: THF: 15 mM pH 2.9 KH2PO4 6:1:1:92 Column temperature: 40 Flow rate: 1.5 Injection volume: 10 Detector: UV 206 CHROMATOGRAM Retention time: 7.5 Internal standard: enalaprilat (10.5) Limit of quantitation: 500 ng/mL KEYWORDS SPE; pharmacokinetics REFERENCE
Wong, Y.-c.; Charles, B.G. Determination of the angiotensin-converting enzyme inhibitor lisinopril in urine using solid-phase extraction and reversed-phase high-performance liquid chromatography. J.Chromatogr.B, 1995, 673, 306-310


Friedman, D.I.; Amidon, G.L. Intestinal absorption mechanism of dipeptide angiotensin converting enzyme inhibitors of the lysyl-proline type: lisinopril and SQ 29,852. J.Pharm.ScL, 1989, 78, 995-998 [rat; perfusate]