Ramipril

Molecular formula: C23H32N2O5

Molecular weight: 416.5
CAS Registry No.: 87333-19-5

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 |xL aliquot of the supernatant. (Buffer was saturated ammonium chloride
solution 25% diluted with water, adjusted to pH 9.5 with 25% ammonia solution.)
HPLC VARIABLES
Column: 300 X 3.9 4 jxm 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: 6.04
Limit of detection: <120 ng/mL
OTHER SUBSTANCES
Extracted: acebutolol, acenocoumarol, acepromazine, acetaminophen, ajmaline, albuterol,
alimemazine, alminoprofen, alpidem, alprazolam, amisulpride, amitriptyline, amodiaquine, amoxapine, aspirin, astemizole, atenolol, benazepril, benperidol, benzocaine, benzoylecgonine, bepridil, betaxolol, bromazepam, brompheniramine, bumadizone, bupivacaine, buprenorphine, buspirone, caffeine, carbamazepine, carbinoxamine, carpipramine,
carteolol, celiprolol, cetirizine, chlorambucil, chlordiazepoxide, chlormezanone, chloroquine, 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, diazoxide, diclofenac, dihydralazine, diphenhydramine, dipyridamole, disopyramide, dosulepine, doxylamine, droperidol, ephedrine, estazolam, etodolac, fenfluramine, fenoprofen, fentiazac, flecainide, floctafenine, flumazenil,
flunitrazepam, fluoxetine, fluphenazine, flurbiprofen, fluvoxamine, glipizide, glutethimide, 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, midazolam, minoxidil, moclobemide, moperone, morphine, nadolol, nalbuphine, nalorphine, naloxone, naltrexone, naproxen, nialamide, nifedipine, niflumic acid,
nimodipine, nitrazepam, nizatidine, 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, propran-

olol, protriptyline, pyrimethamine, quinidine, quinine, quinupramine, ranitidine, ritodrine, secobarbital, sotalol, strychnine, sulfinpyrazole, sulindac, sulpride, sultopride,
suriclone, temazepam, tenoxicam, terbutaline, terfenadine, tetrazepam, thiopental,
thioproperazine, thioridazine, tianeptine, tiapride, tiaprofenic acid, ticlopidine, timolol,
tioclomarol, tofisopam, tolbutamide, toloxatone, trazodone, triazolam, trifluoperazine, trifluperidol, trimipramine, triprolidine, tropatenine, verapamil, viloxazine, vincristine, vindesine, warfarin, yohimbine, zolpidem, zopiclone, zorubicine
Interfering: aceprometazine, aconitine, alprenolol, bisoprolol, chlorophenacinone, diazepam, diltiazem, doxepin, glibenclamide, glibornuride, haloperidol, mianserine, nicardipine, nitrendipine, reserpine, tetracaine, vinblastine
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
Sample preparation: Water, apple juice. Centrifuge at 350 g for 10 min, filter (0.45 |xm)
the supernatant, dilute the nitrate with 1-2 volumes of water, inject a 50 |xL aliquot.
Applesauce. 1 g Applesauce + 5 mL 100 mM HCl, vortex for 2 min, centrifuge at 350 g
for 10 min, filter (0.45 |xm) the supernatant, dilute the nitrate with 1-2 volumes of water,
inject a 50 jxL aliquot.
HPLCVARIABLES
Column: C18 (J.T. Baker)
Mobile phase: MeCNibuffer 38.5:61.5, adjusted to pH 2.1 0.1 with concentrated phosphoric acid (Buffer was 14 g sodium perchlorate monohydrate and 100 mL 500 mM phosphoric acid made up to 1 L with water, pH adjusted to 2.5 0 . 1 with triethylamine.)
Flow rate: 1
Injection volume: 50
Detector: UV 210
CHROMATOGRAM
Retention time: 12.1
Limit of detection: 100 ng/mL
OTHER SUBSTANCES
Simultaneous: impurities, degradation products
KEYWORDS
water; apple juice; applesauce; stability-indicating
REFERENCE
Allen, L.V., Jr.; Stiles, M.L.; Prince, S.J.; McLaury, H.-J.; Sylvestri, M.R Stability of ramipril in water,
apple juice, and applesauce. Am.J.Health-Syst.Pharm., 1995, 52, 2433-2436

SAMPLE
Matrix: solutions
HPLCVARIABLES
Column: 250 X 4.6 Spherisorb 5 ODS-2
Mobile phase: n-Propanol:buffer 20:80 (Buffer was pH 3.0 phosphate buffer containing
0.4% triethylamine.)

Flow rate: 1
Detector: UV 240
CHROMATOGRAM
Retention time: 16
OTHER SUBSTANCES
Simultaneous: benzepril, captopril, cilazapril, enalapril, quinapril
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 55:45:0.05
Detector: UV 215-220
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: solutions
HPLCVARIABLES
Column: 5 jxm Nucleosil SA
Mobile phase: MeCN:buffer 2:1 (Buffer was 0.15% KH2PO4 adjusted to pH 3.0 with phosphoric acid.)
Flow rate: 1
Detector: UV 210
CHROMATOGRAM
Retention time: 13
OTHER SUBSTANCES
Simultaneous: impurities, diastereomer (RS-SSS)
REFERENCE
Ito, M.; Kuriki, T.; Goto, J.; Nambara, T. Separation of ramipril optical isomers by high-performance
liquid chromatography. J.Liq.Chromatogr., 1990, 13, 991-1000

SAMPLE
Matrix: solutions
HPLCVARIABLES
Column: Nucleosil 5 C18
Mobile phase: MeOH-.buffer 50:50 (Buffer was 0.15% KH2PO4 adjusted to pH 2.4 with
phosphoric acid.)

Flow rate: 1
Detector: UV 210
CHROMATOGRAM
Retention time: k' 10.60
OTHER SUBSTANCES
Simultaneous: impurities, diastereomers (SS-RRR, RS-RRR, SR-SSS)
REFERENCE
Ito, M.; Kuriki, T.; Goto, J.; Nambara, T. Separation of ramipril optical isomers by high-performance
liquid chromatography. J.Liq.Chromatogr., 1990, 13, 991-1000