Sertraline

Molecular formula: C17H17CI2N

Molecular weight: 306.2
CAS Registry No.: 79617-96-2 (sertraline), 79559-97-0 (sertraline hydrochloride)

SAMPLE
Matrix: blood
Sample preparation: Condition a 1 mL Bond Elut C18 SPE cartridge with 1 M HCl, twice
with MeOH5 and once with water. 500 \xL Serum + 200 JJLL 500 ng/mL IS in 10 mg/mL
potassium bicarbonate + 500 fxL MeCN, centrifuge, add to the SPE cartridge, wash twice
with water, wash once with MeCN, elute (by gravity) with 250 (xL MeOH containing 25
mL/L 35% perchloric acid, inject a 20 |xL aliquot of the eluate.

HPLCVARIABLES
Column: 150 X 4.6 5 |xm Ultrasphere ODS
Mobile phase: MeCN: water: 7% perchloric acid 400:750:0.5 containing 0.5 g tetramethy-
lammonium perchlorate
Flow rate: 1.8
Injection volume: 20
Detector: UV 205

CHROMATOGRAM
Retention time: 11
Internal standard: CP-53,630-1 (8)
Limit of quantitation: 10 ng/mL

OTHER SUBSTANCES
Simultaneous: desmethylsertraline

KEYWORDS
serum; SPE

REFERENCE
Gupta, R.N.; Dziurdzy, S.A. Therapeutic monitoring of sertraline. Clin.Chem., 1994, 40, 498-499

SAMPLE
Matrix: blood
Sample preparation: 1 mL Blood + 100 jxL 1 |jig/mL metycaine + 1 mL pH 9 saturated
potassium borate buffer, mix, add 5 mL butyl chloride, extract. Remove the organic layer
and add it to 1 mL 100 mM sulfuric acid, extract. Remove the aqueous layer and basify
it with concentrated ammonium hydroxide, add 50 |xL chloroform, extract. Remove the
chloroform layer, evaporate to dryness under air at 60, reconstitute in 100 fxL MeOH,
inject a 20 jxL aliquot.

HPLCVARIABLES
Column: Lichrospher RP-8
Mobile phase: MeCN: 50 mM pH 3 phosphate buffer 45:55
Flow rate: 1.5
Injection volume: 20
Detector: UV 230

CHROMATOGRAM
Retention time: 6.3
Internal standard: metycaine (4)
Limit of quantitation: 50 ng/mL

OTHER SUBSTANCES
Simultaneous: desmethylsertraline, diphenhydramine

REFERENCE
Logan, B.K.; Friel, RN.; Case, G.A. Analysis of sertraline (Zoloft) and its major metabolite in postmortem
specimens by gas and liquid chromatography. J.Anal.ToxicoL, 1994, 18, 139142

SAMPLE
Matrix: blood
Sample preparation: Condition a 200 mg 10 mL Clean Screen copolymeric ZSDAU020
SPE cartridge with 3 mL MeOH, 3 mL water, and 1 mL 100 mM pH 6 KH2PO4. 1 mL
Serum + 2mL 100 mM pH 6 KH2PO4 + 250 |xL 2 ^g/mL protriptyline, add to the SPE
cartridge, wash with 1 mL water, wash with 1 mL 1 M acetic acid, wash with 3 mL MeOH,
dry under vacuum for 5 min, elute with 3 mL dichloromethane: isopropanol: ammonium
hydroxide 78:20:2. Add a drop of diethylamine to the eluate and evaporate it to dryness
at 40 under a stream of nitrogen. Reconstitute the residue in 100 |xL mobile phase, inject
a 50 JULL aliquot.

HPLCVARIABLES
Column: 150 X 4.6 5 \xm Supelco LC-8
Mobile phase: MeCN: MeOH: water: diethylamine 1000:800:1200:2, containing 1.5 g so-
dium pentanesulfonate, pH adjusted to 5.5-6.0 with phosphoric acid
Flow rate: 1.5
Injection volume: 50
Detector: UV 600 for 2 min then UV 214

CHROMATOGRAM
Retention time: 9
Internal standard: protriptyline (6)
Limit of detection: 10 ng/mL

OTHER SUBSTANCES
Simultaneous: desmethylsertraline

KEYWORDS
serum; SPE

REFERENCE
Rogowsky, D.; Marr, M.; Long, G.; Moore, C. Determination of sertraline and desmethylsertraline in
human serum using copolymeric bonded-phase extraction, liquid chromatography and gas chroma-
tography-mass spectrometry. J.Chromatogr.B, 1994, 655, 138-141

SAMPLE
Matrix: blood
Sample preparation: 1 mL Plasma + 1 mL 0.6 M pH 9.8 carbonate buffer + 40 |xL 5
|xg/mL maprotiline in 10 mM HCl + 5 mL 200 g/L ethyl acetate in n-heptane, mix by
rocking for 10 min, centrifuge at 1500 g for 10 min. Remove organic layer and add it to
150 |JLL 100 mM HCl, mix 10 min, centrifuge at 1500 g for 10 min. Discard organic layer
 and evaporate aqueous layer at 45 in a vacuum centrifuge for 1 h. Take up residue in
50 |xL 1 M pH 10.3 carbonate buffer and 25 |xL 10 mg/mL dansyl chloride in MeCN,
vortex, allow to react at room temperature for 45 min, evaporate at 45 in a vacuum
centrifuge for 20 min, reconstitute in 125 |xL MeCN: water 75:25, vortex, centrifuge for
3-5 min, inject a 25-40 JJLL aliquot.

HPLCVARIABLES
Column: 250 X 4.6 5 |xm Supelcosil LC-18
Mobile phase: MeCN: 25 mM KH2PO4 75:25 containing 500 |xL/L orthophosphoric acid and
600 |xL/L n-butylamine
Flow rate: 2
Injection volume: 25-40
Detector: F ex 235 em 470 (cut-off)

CHROMATOGRAM
Retention time: 25.60
Internal standard: maprotiline (12.8)

OTHER SUBSTANCES
Simultaneous: amoxapine, clovoxamine, desipramine, fenfluramine, fluoxetine, fluvoxam-
ine, norfluoxetine, nortriptyline, propranolol, protriptyline
Noninterfering: amitriptyline, atenolol, bupropion, carbamazepine, chlordiazepoxide, ci-
talopram, clomipramine, clozapine, cyclobenzaprine, doxepin, imipramine, loxapine, me-
toprolol, mianserin, moclobemide, nomifensine, pindolol, thioridazine, tranylcypromine,
trazodone, trimipramine

KEYWORDS
plasma

REFERENCE
Suckow, R.F.; Zhang, M.R; Cooper, T.B. Sensitive and selective liquid-chromatographic assay of fluoxe-
tine and norfluoxetine in plasma with fluorescence detection after precolumn derivatization.
Clin.Chem., 1992, 38, 1756-1761

SAMPLE
Matrix: solutions

HPLC VARIABLES
Column: 250 X 4.6 5 \xm Supelcosil LC-DP (A) or 250 X 4 5 |xm 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: 14.50 (A), 7.68 (B)

OTHER SUBSTANCES
Also analyzed: acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine,
albuterol, alprazolam, amitriptyline, amobarbital, amoxapine, antipyrine, atenolol, atro-
pine, azatadine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam,
bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine,
chlorcyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine,
chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimeti-
 dine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchi-
cine, cyclizine, cyclobenzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal,
diltiazem, diphenhydramine, diphenidol, diphenoxylate, dipyridamole, disopyramide, do-
butamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine,
fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvox-
amine, furosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hy-
dralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydroxychloroquine, hydro-
xyzine, 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, na-
phazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, ox-
ycodone, 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, propofol, propran-
olol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxi-
pride, risperidone, salicylic acid, scopolamine, secobarbital, sotalol, spironolactone, sulfin-
pyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline,
thiethylperazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide,
tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimepra-
zine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine,
zopiclone

KEYWORDS
some details of plasma extraction

REFERENCE
Koves, E.M. Use of high-performance liquid chromatography-diode array detection in forensic toxicology.
J.Chromatogr.A, 1995, 692, 103-119

SAMPLE
Matrix: tissue
Sample preparation: Homogenize 1 mL liver in 5 mL water. Centrifuge 1 mL homogenate,
add the supernatant to 1.2 \xg clomipramine, add 75 |xL MeOH, add 75 |JLL MeCN, add
100 |xL 1 M HCl, vortex, centrifuge, inject an aliquot of the supernatant.

HPLCVARIABLES
Column: 300 X 3.9 ^Bondapak C18
Mobile phase: MeCN: 50 mM potassium phosphate buffer 35:65
Flow rate: 1.3
Detector: UV 213

CHROMATOGRAM
Internal standard: clomipramine

OTHER SUBSTANCES
Extracted: metabolites, desmethylsertraline
Also analyzed: fluoxetine

KEYWORDS
mouse; liver
REFERENCE
von Moltke, L.L.; Greenblatt, D.J.; Cotreau-Bibbo, M.M.; Duan, S.X.; Harmatz, J.S.; Shader, R.L Inhi-
bition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor antidepressants and by
quinidine and ketoconazole: A model system to predict drug interactions in vivo. J.Phar-
macol.Eocp.Tker., 1994,268, 1278-1283

SAMPLE
Matrix: tissue
Sample preparation: 130 mg Brain tissue + 1.1 mL EtOH + 3.3 |xg tetracaine hydro-
chloride, disrupt by sonication, centrifuge, inject a 20 |JLL aliquot.

HPLC VARIABLES
Column: 300 X 4.1 10 |xm Versapack C18
Mobile phase: MeCN: 250 mM pH 2.7 potassium phosphate buffer 30:70
Flow rate: 2
Injection volume: 20
Detector: UV 235

CHROMATOGRAM
Retention time: 12
Internal standard: tetracaine hydrochloride (4.9)
Limit of detection: 6.12 \xg/g

OTHER SUBSTANCES
Extracted: desmethylsertraline

KEYWORDS
brain; mouse

REFERENCE
Wiener, H.L.; Kramer, H.K.; Reith, M.E.A. Separation and determination of sertraline and its metabo-
lite, desmethylsertraline, in mouse cerebral cortex by reversed-phase high-performance liquid chro-
matography. J.Chromatogr., 1990, 527, 467-472