Quinapril

Molecular formula: C25H30N2O5

Molecular weight: 438.5
CAS Registry No.: 85441-61-8 (quinapril),
90243-99-5 (quinapril hydrochloride monohydrate),
82586-55-8 (quinapril hydrochloride)

SAMPLE
Matrix: blood, urine
Sample preparation: Condition a 100 mg 1 mL Bond-Elut C18 SPE cartridge with two 1
mL portions of MeOH, two 1 mL portions of water, and two 1 mL portions of 100 mM
HCl. Condition a CBA-Bond-Elut SPE cartridge with MeOH and water. 1 mL Plasma +
1 mL buffer + 250 ng IS (or 50-500 jxL urine + 500 ng IS), add to the C18 SPE cartridge,
wash with two 1 mL portions of pH 3.4 water, wash with two 1 mL portions of distilled
n-hexane, dry under vacuum for 20-30 min, elute with three 1 mL portions of
chloroform: MeOH 2:1. Evaporate the eluate to dryness, reconstitute with 50 |xL
chloroform: MeOH 50:50 and 50 |xL 2 mg/mL 9-anthryldiazomethane in MTBE, vortex
for a few s, heat at 40 for 90 min, evaporate to dryness, reconstitute with two 100 JJLL
portions of MeCN, add to the CBA SPE cartridge, wash with two 1 mL portions of MeCN,
elute with three 1 mL portions of MeCN: triethylamine 99.8:0.2, evaporate the eluate to
dryness under reduced pressure, reconstitute with 200 |JLL MeCN, inject a 20-50 (xL aliquot. (Prepare 9-anthryldiazomethane as follows. Stir 8.8 g 9-anthraldehyde and 8.5 g
80% hydrazine hydrate (Caution! Hydrazine hydrate is a carcinogen!) in 150 mL EtOH
at room temperature for 3 h, filter off the solid 9-anthraldehyde hydrazone and dry under
vacuum (mp 124-6) (Bull. Chem. Soc. Jpn. 1967, 40, 691). Dissolve 220 mg 9-anthraldehyde hydrazone in 100 mL anhydrous ether, add 800 mg activated manganese dioxide,
follow the reaction by reverse-phase HPLC using MeCN at 0.4 mL/min and UV 254. At
the end of the reaction filter off the manganese and wash it with 20 mL ether, evaporate
the filtrate to obtain 9-anthryldiazomethane (mp 64-6) (Anal.Biochem. 1980, 107, 116
and 1983, 132 456). Prepare activated manganese dioxide as follows. Stir a solution of 20
g potassium permanganate in 250 mL water at room temperature, add 1Og activated
carbon (Nuchar C-190 or C-190N), stir for 16 h, filter (Buchner funnel), wash 4 times
with 50 mL portions of water, dry in air, dry in an oven at 105-110 for 8-24 h
(J.Org.Chem. 1970, 35, 3971).)
HPLCVARIABLES
Column: 125 X 4.6 5 |xm Spherisorb ODS II
Mobile phase: MeCN: MeOH: water 45:40:15 containing 0.24% ammonium perchlorate
and 0.02% triethylamine
Flow rate: 1.6
Injection volume: 20-50
Detector: F ex 360 em 440
CHROMATOGRAM
Retention time: 3.8
Internal standard: [2S-[l[R*(R*)]],2R*]-l-[2-[[(l-carboxy-3-phenyl)propyl]amino]-l-oxopropyl]-octahydro-lH-indole-2-carboxylicacid (PD 110021, Warner-Lambert) (16)
Limit of detection: 5 ng/mL (plasma)
Limit of quantitation: 20 ng/mL (plasma); 100 ng/mL (urine)
OTHER SUBSTANCES
Extracted: metabolites, quinaprilat
Simultaneous: enalapril, enalaprilat
KEYWORDS
plasma; derivatization; pharmacokinetics; SPE

REFERENCE
Hengy, H.; Most, M. Determination of the new ACE-inhibitor quinapril and its active metabolite quinaprilate in plasma and urine by high-performance liquid chromatography and pre-column labelling
for fluorescent-detection. J.Liq.Chromatogr., 1988, 11, 517-530

SAMPLE

Matrix: perfusate
Sample preparation: Add taurocholic acid to perfusate, filter, inject an aliquot.
HPLCVARIABLES

Column: 5 |xm Ultrasphere C18

Mobile phase: MeOH: 50 mM pH 7.4 sodium phosphate buffer 70:30
Detector: UV 220
CHROMATOGRAM

Retention time: 5.5

Internal standard: taurocholic acid (7.5)
REFERENCE
Hu, M.; Zheng, L.; Chen, J.; Liu, L.; Zhu, Y; Dantzig, A.H.; Stratford, R.E., Jr. Mechanisms of transport
of quinapril in Caco-2 cell monolayers: Comparison with cephalexin. Pharm.Res., 1995, 12, 11201125

SAMPLE

Matrix: perfusate, urine

Sample preparation: 100 \xL Urine or perfusate + 200 |xL MeCN, vortex for 5 s, sonicate
for 5 min, centrifuge at 11150 g for 5 min, inject a 100 ^xL aliquot.
HPLCVARIABLES

Guard column: 10 mm long 5 |xm Econosil C8

Column: 250 X 4.6 5 imm Econosil C8
Mobile phase: MeCN:buffer 55:45 (Buffer was 0.01% triethylamine adjusted to pH 2.00
with phosphoric acid.)
Flow rate: 1
Injection volume: 100
Detector: UV 215; Radioactivity
CHROMATOGRAM

Retention time: 3.4

OTHER SUBSTANCES

Extracted: metabolites, quinaprilat

KEYWORDS

tritium labelled; dog; pharmacokinetics

REFERENCE
Kugler, A.R.; Olson, S.C; Smith, D.E. Determination of quinapril and quinaprilat by high-performance
liquid chromatography with radiochemical detection, coupled to liquid scintillation counting spectrometry. J.Chromatogr.B, 1995, 666, 360-367

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: 22
OTHER SUBSTANCES

Simultaneous: benzepril, captopril, cilazapril, enalapril, ramipril

REFERENCE
Barbato, F.; Morrica, P.; Quaglia, F. Analysis of ACE inhibitor drugs by high performance liquid chromatography Farmaco, 1994, 49, 457-460