Propofol

Molecular formula: C12H18O

Molecular weight: 178.3
CAS Registry No.: 2078-54-8

SAMPLE
Matrix: blood
Sample preparation: 1 ml Whole blood + 20 JULL thymol in MeOH + 1 mL 100 mM
NaH2PO4 + 5 mL cyclohexane, shake at 200 rpm for 15 min, centrifuge at 1200 g for 5
min. Remove 4.5 mL of the organic layer and add it to 50 |JLL 1.875% tetraethylammonium
hydroxide in EtOH, evaporate to dryness under a stream of nitrogen, reconstitute the
residue in mobile phase, inject an aliquot.
HPLCVARIABLES
Column: 250 X 4 C18
Mobile phase: MeCN: buffer 67:33 (Buffer was water adjusted to pH 4.0 with acetic acid.)
Detector: UV
CHROMATOGRAM
Retention time: 13
Internal standard: thymol (5-methyl-2-isopropylphenol) (8)
Limit of quantitation: 500 ng/mL
KEYWORDS
whole blood; pharmacokinetics
REFERENCE
Dawidowicz, A.L.; Fijalkowska, A. Determination of propofol in blood by HPLC. Comparison of the
extraction and precipitation methods. J.Chromatogr.Sci., 1995, 33, 377-382

SAMPLE
Matrix: blood
Sample preparation: Condition a 1 mL Supelclean LC-18 SPE cartridge (Supelco) with
two 1 mL portions of MeCN and two 1 mL portions of water. 50 |xL Whole blood + 25 ng
thymol + 200 |xL 100 mM KH2PO4, mix, add to the SPE cartridge, wash with two 1 mL
portions of water, elute with MeCN. Discard the first 50 jxL eluate and collect the next
600 (xL, evaporate to about 200 jxL under a stream of nitrogen, inject a 30 |xL aliquot.
HPLCVARIABLES
Guard column: Chrompack RP guard column
Column: 100 X 4.6 5 p,m Spherisorb S5ODS2
Mobile phase: MeCN: water: 85% orthophosphoric acid 46:54:0.1
Flow rate: 1
Injection volume: 30
Detector: F ex 276 em 310
CHROMATOGRAM
Internal standard: thymol
Limit of quantitation: 50 ng/mL
KEYWORDS
whole blood; SPE; pharmacokinetics

REFERENCE
Lee, H.-S.; Khoo, Y-M.; Chua, B.-C; Ng, A.S.-B.; Tan, S.S.-W.; Chew, S.-L. Pharmacokinetics of propofol
infusion in Asian patients undergoing coronary artery bypass grafting. Ther.Drug Monit., 1995, 17,
336-341

SAMPLE

Matrix: blood
Sample preparation: 500 |xL Serum + 500 |xL 20 \iglmL dibutyl phthalate in MeCN: 65%
perchloric acid 67:33, vortex for 1 min, centrifuge at 1150 g for 5 min, inject a 20 |xL
aliquot of the supernatant.
HPLCVARIABLES

Column: 250 X 4.6 10 |xm Spherisorb C18

Mobile phase: MeCN: water: acetic acid 67:33:0.04, pH 4.0
Flow rate: 1.5
Injection volume: 20
Detector: UV 270
CHROMATOGRAM

Internal standard: dibutyl phthalate

Limit of detection: 100 ng/mL
KEYWORDS

serum
REFERENCE
Pavan, L; Buglione, E.; Massiccio, M.; Gregoretti, C; Burbi, L.; Berardino, M. Monitoring propofol serum
levels by rapid and sensitive reversed-phase high-performance liquid chromatography during prolonged sedation in ICU patients. J.Chromatogr.Sci., 1992, 30, 164-166

SAMPLE

Matrix: blood, urine

Sample preparation: Inject a 10-400 |xL aliquot of serum or urine onto column A with
mobile phase A and elute to waste, after 2 min backflush the contents of column A onto
column B with mobile phase B, elute with mobile phase B, monitor the effluent from
column B.
HPLC VARIABLES

Column: A 20 X 4 37-50 |xm Bondapak C18/Corasil; B 125 X 4 5 |xm LiChrosorb RP-18

Mobile phase: A 10 mM pH 7.88 KH2PO4; B MeCN: 10 mM pH 7.88 KH2PO4 70:30
Flow rate: A 1.5; B 1.3
Injection volume: 10-400
Detector: F ex 276 em 310
CHROMATOGRAM

Retention time: 5
Limit of quantitation: 5 ng/mL
KEYWORDS

serum; column-switching
REFERENCE
Altmayer, P.; Biich, U.; Buch, H.R; Larsen, R. Rapid and sensitive pre-column extraction high-performance liquid chromatographic assay for propofol in biological fluids. J.Chromatogr., 1993, 612,
326-330

SAMPLE
Matrix: formulations
Sample preparation: Filter (0.45 |xm). Add an aliquot to an aliquot of 1 mg/mL thymol,
make up to 3 mL with MeOH, inject a 50 jxL aliquot.
HPLCVARIABLES
Column: 250 X 4.6 5 |xm Hypersil ODS C18
Mobile phase: MeCN: MeOH: water 55:10:35
Flow rate: 2
Injection volume: 50
Detector: UV 270
CHROMATOGRAM
Retention time: 7.5
Internal standard: thymol (4.0)
KEYWORDS
stability-indicating; parenteral nutrient solutions
REFERENCE
Bhatt-Mehta, V.; Paglia, R.E.; Rosen, D.A. Stability of propofol with parenteral nutrient solutions during
simulated Y-site injection. Am. J.Health-Syst.Pharm., 1995, 52, 192-196

SAMPLE
Matrix: solutions
HPLCVARIABLES
Column: 250 X 4.6 5 |xm Supelcosil LC-DP (A) or 250 X 4 5 ^m LiChrospher 100 RP-8 (B)
Mobile phase: MeCN:0.025% phosphoric acid:buffer 25:10:5 (A) or 60:25:15 (B) (Buffer
was 9 mL concentrated phosphoric acid and 10 mL triethylamine in 900 mL water, adjust
pH to 3.4 with dilute phosphoric acid, make up to 1 L.)
Flow rate: 0.6
Injection volume: 25
Detector: UV 229
CHROMATOGRAM
Retention time: 10.07 (A), 15.24 (B)
OTHER SUBSTANCES
Also analyzed: acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine,
albuterol, alprazolam, amitriptyline, amobarbital, amoxapine, antipyrine, atenolol, atropine, azatadine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam,
bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine,
chlorcyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine,
chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, eolchicine, cyclizine, cyclobenzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal,
diltiazem, diphenhydramine, diphenidol, diphenoxylate, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine,
fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, furosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydroxychloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac,
labetalol, levorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol,
mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol,
metformin, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine,

methoxamine, methyldopa, methylphenidate, metoclopramide, metolazone, metoprolol,

metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazoline, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline,
perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine,
phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine,
prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine,
promazine, promethazine, propafenone, propantheline, propiomazine, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline,
thiethylperazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide,
tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine,
zopiclone
KEY WORDS
some details of plasma extraction
REFERENCE
Koves, E.M. Use of high-performance liquid chromatography-diode array detection in forensic toxicology.
J.ChromatogrA, 1995, 692, 103-119

ANNOTATED BIBLIOGRAPHY
Fan, S.Z.; Yu, H.Y.; Chen, YL.; Liu, CC. Propofol concentration monitoring in plasma or whole blood
by gas chromatography and high-performance liquid chromatography. Anesth.Analg., 1995, 81,
175-178
Bailey, L.C; Tang, K.T.; Rogozinski, B.A. The determination of 2,6-diisopropylphenol (propofol) in an oil
in water emulsion dosage form by high-performance liquid chromatography and by second derivative
UV spectroscopy. J.Pharm.Biomed.AnaL, 1991, 9, 501-506
Chan, K.; So, A.P. The measurement of propofol in human blood samples by liquid chromatography.
Methods Find.Exp.CUn.Pharmacol, 1990, 12, 135-139
Mazzi, G.; Schinella, M. Simple and practical high-performance liquid chromatographic assay of propofol
in human blood by phenyl column chromatography with electrochemical detection. J.Chromatogr.,
1990, 528, 537-541