Analisi dei farmaci: via il dente via il dolore con la colonna LC Raptor bifenilica

• 231 composti, più di 40 isobari, 10 classi di farmaci e 22 composti ESI in 10 minuti utilizzando 1 colonna.
• Una colonna LC SPP Raptor, grazie alla selettività bifenilica targata Restek, testata e consolidata nel tempo, è la colonna LC più versatile e adatta alle analisi multiclasse disponibile sul mercato.
• Separazione eccellente degli isobari più critici senza scodamento del picco.
• Analisi LC-MS/MS veloci, affidabili e ad alto rendimento, con maggiore sensibilità utilizzando fasi mobili semplici.

Il consumo di antidolorifici è in costante aumento. Di conseguenza, i laboratori ospedalieri e privati ricevono sempre più campioni di screening per un ampio spettro di antidolorifici, per prevenire l’abuso di farmaci e garantire la sicurezza dei pazienti e il rispetto del loro regime terapeutico. Il monitoraggio terapeutico dei farmaci può essere complicato a causa dei valori soglia bassi, delle potenziali interferenze della matrice e dei composti isobarici di farmaci. Per affrontare queste sfide, molte strutture che effettuano test sui prodotti medicinali stanno passando alla cromatografia liquida abbinata alla spettrometria di massa (LC-MS/MS) per la sua maggiore velocità, sensibilità e specificità. 

Come mostra l’analisi di seguito, la colonna Raptor bifenilica di Restek è ideale per sviluppare metodologie LC-MS/MS efficaci per lo screening degli antidolorifici. Grazie alla ritenzione estremamente elevata e alla selettività unica è possibile analizzare in soli 10 minuti 231 composti di farmaci multiclasse e metaboliti, tra cui oltre 40 isobari. Inoltre sono stati ottimizzati per la colonna Raptor bifenilica test tossicologici specifici per oppioidi, ansiolitici, barbiturici, FANS e analgesici, antidepressivi, antipilettici, antipsicotici, allucinogeni, e stimolanti, da utilizzare durante le analisi quantitative e di conferma.

	Peaks	tR (min)	Conc. (ng/mL)	Precursor Ion	Product Ion	Product Ion
1.	trans-3-Hydroxycotinine	1.32	25	193.1	80.0	134.0
2.	Norcotinine	1.33	25	163.1	80.1	118.1
3.	Nicotine	1.40	25	163.2	130.1	117.1
4.	BZP	1.47	25	177.2	91.1	65.1
5.	Anabasine	1.53	25	163.2	120.1	80.1
6.	Noroxymorphone	1.78	25	288.1	270.1	212.9
7.	Lisdexamfetamine	1.79	25	264.2	84.1	91.0
8.	Phenelzine sulfate	1.90	25	137.2	105.1	77.1
9.	Acetaminophen	1.93	100	152.2	93.0	65.0
10.	Pregabalin	2.21	25	160.2	142.1	55.0
11.	Cotinine	2.27	25	177.2	80.0	98.1
12.	Morphine	2.27	25	286.2	152.1	165.0
13.	(+)-Ephedrine	2.37	25	166.2	148.1	115.0
14.	Oxymorphone	2.38	25	302.1	227.2	198.2
15.	Hydromorphone	2.61	25	286.2	184.9	156.9
16.	Amphetamine	2.63	25	136.2	91.0	65.1
17.	DMAA	2.65	25	116.1	57.1	99.2
18.	Gabapentin	2.71	25	172.2	154.0	137.1
19.	Methylephedrine	2.83	25	180.2	162.0	115.1
20.	Levetiracetam	2.84	25	171.1	125.9	69.2
21.	Desmethylolanzapine	2.94	25	299.1	256.1	198.0
22.	Norcodeine	2.96	25	286.1	151.9	115.0
23.	Olanzapine	3.12	25	313.2	256.1	198.1
24.	Methamphetamine	3.13	25	150.3	91.1	119.0
25.	MDA	3.18	25	180.1	163.1	105.2
26.	(-)-Naloxone	3.27	25	328.3	310.1	212.3
27.	Phentermine	3.29	25	150.2	91.1	133.1
28.	Noroxycodone	3.32	25	302.1	227.0	197.9
29.	Methylone	3.36	25	208.1	160.1	132.1
30.	O-Desmethyl-cis-tramadol	3.37	25	250.1	58.0	42.0
31.	(-)-Dihydrocodeine	3.38	25	302.2	199.0	128.2
32.	Norhydrocodone	3.43	25	286.1	199.0	128.2
33.	Codeine	3.43	25	300.2	152.0	165.1
34.	6-Acetylmorphine	3.47	25	328.2	165.0	211.0
35.	MDMA	3.60	25	194.2	163.0	135.1
36.	Desomorphine	3.61	25	272.1	152.1	165.0
37.	Oxycodone	3.64	25	316.2	298.0	169.0
38.	Naltrexone	3.71	25	342.2	324.0	267.0
39.	Levamisole	3.75	25	205.1	178.0	91.1
40.	Hydrocodone	3.76	25	300.1	199.0	128.0
41.	Diethylpropion	3.80	25	206.2	105.1	100.1
42.	Mephedrone	3.80	25	178.2	145.0	160.1
43.	2-Oxo-3-hydroxy-LSD	3.82	25	356.3	237.0	222.0
44.	o-Desmethylvenlafaxine	3.84	25	264.1	58.1	107.0
45.	6-β-Naltrexol	3.91	25	344.3	326.1	308.1
46.	Tapentadol-β-D-glucuronide	3.91	25	398.3	222.1	107.0
47.	7-Aminonitrazepam	3.95	25	252.2	121.1	94.2
48.	MDEA	4.00	25	208.1	163.0	105.2
49.	m-Hydroxybenzoylecgonine	4.02	25	306.1	168.1	121.0
50.	Lamotrigine	4.09	25	256.0	211.1	145.0
51.	Ritalinic acid	4.11	25	220.1	84.1	56.2
52.	N-Desmethyltapentadol	4.16	25	208.1	121.2	107.1
53.	Norbuprenorphine glucuronide	4.18	25	590.5	414.3	165.0
54.	Zonisamide	4.23	25	212.9	132.1	77.1
55.	mCPP	4.26	25	197.1	154.0	118.1
56.	Norketamine	4.28	25	224.1	125.0	89.1
57.	Nalbuphine	4.33	25	358.2	340.1	115.0
58.	Norfentanyl	4.33	25	233.1	84.1	55.0
59.	(+/-)-Hydroxybupropion	4.35	25	256.0	130.2	166.0
60.	Tapentadol	4.37	25	222.1	107.1	121.0
61.	Lacosamide	4.47	25	251.5	91.1	108.1
62.	Dextrorphan	4.50	25	258.2	157.0	201.2
63.	Levorphanol	4.50	25	258.2	156.8	199.2
64.	7-Hydroxyquetiapine	4.51	25	400.3	269.0	208.0
65.	Molindone	4.51	25	277.2	100.1	70.2
66.	Tramadol	4.52	25	264.2	58.0	77.1
67.	Zolpidem phenyl-4-carboxylic acid	4.60	25	338.2	265.1	219.0
68.	Felbamate	4.62	25	239.1	117.1	177.8
69.	N-Desmethyl-cis-tramadol	4.65	25	250.2	44.0	232.1
70.	Ketamine	4.66	25	238.1	125.1	89.1
71.	Benzoylecgonine	4.67	25	290.1	168.1	77.1
72.	Methylphenidate	4.68	25	234.1	84.1	56.1
73.	Normeperidine	4.76	25	234.1	160.2	91.0
74.	Meprobamate	4.79	25	219.1	158.2	97.0
75.	Meperidine	4.80	25	248.1	220.1	174.1
76.	Bupropion	4.81	25	240.0	184.1	130.2
77.	Heroin	4.85	25	370.4	328.2	164.9
78.	Cocaine	5.01	25	304.2	182.0	77.1
79.	7-Aminoclonazepam	5.02	25	286.1	121.2	250.1
80.	Zopiclone	5.04	25	389.2	245.0	217.2
81.	N-Desmethylmirtazapine	5.10	25	252.1	195.1	209.2
82.	Norcocaine	5.11	25	290.1	168.0	136.1
83.	Phenobarbital*	5.11	500	230.9	187.8	85.0
84.	Buprenorphine glucuronide	5.12	25	644.3	468.2	55.1
85.	MDPV	5.15	25	276.2	135.1	126.1
86.	Venlafaxine	5.15	25	278.4	260.4	121.2
87.	Milnacipran	5.24	25	247.2	100.1	129.1
88.	Pentazocine	5.29	25	286.2	218.1	69.2
89.	Mirtazapine	5.31	25	266.1	195.1	72.1
90.	Butalbital*	5.31	500	223.0	180.0	84.9
91.	Norbuprenorphine	5.35	50	414.3	152.2	165.2
92.	LSD	5.39	25	324.3	223.1	208.0
93.	Butorphanol	5.43	25	328.3	310.3	131.2
94.	Fosphenytoin	5.43	25	363.1	265.9	207.8
95.	Topiramate	5.44	25	340.2	264.2	223.9
96.	Cocaethylene	5.48	25	318.2	196.1	82.0
97.	Clozapine	5.48	25	328.2	271.1	193.1
98.	9-Hydroxyrisperidone	5.51	25	427.3	207.1	110.2
99.	Acetyl fentanyl	5.58	25	323.3	188.0	105.0
100.	Didesmethyl citalopram HCl	5.73	25	297.1	261.9	109.1
101.	7-Aminoflunitrazepam	5.75	25	284.1	135.0	227.1
102.	Amobarbital*	5.75	500	225.0	182.0	84.8
103.	Zolpidem	5.76	25	308.2	235.2	218.9
104.	N-Desmethylcitalopram	5.77	25	311.1	262.1	109.1
105.	Isocarboxazid	5.77	25	232.0	91.1	65.2
106.	Pentobarbital*	5.79	500	225.0	182.0	84.9
107.	Escitalopram	5.80	25	325.3	109.1	261.9
108.	Citalopram	5.80	25	325.2	109.1	262.0
109.	Diphenhydramine	5.80	25	256.1	167.0	152.1
110.	Desmethyldoxepin	5.88	25	266.1	107.1	115.0
111.	Ezogabine	5.91	25	304.0	230.1	109.1
112.	Doxepin	5.96	25	280.1	107.2	77.1
113.	Haloperidol	5.96	25	377.2	123.0	95.1
114.	Fluvoxamine	5.97	25	319.3	71.1	257.8
115.	Trazodone	5.99	25	372.3	176.1	148.0
116.	Norfluoxetine	6.01	25	296.3	134.3	104.9
117.	Fentanyl	6.02	25	337.3	188.0	105.1
118.	Oxcarbazepine	6.02	25	253.1	180.0	208.1
119.	Risperidone	6.03	25	411.2	191.0	110.1
120.	Buprenorphine	6.04	50	468.3	55.1	414.2
121.	Fluoxetine	6.05	25	310.1	148.0	115.1
122.	Secobarbital*	6.08	500	237.0	193.9	84.8
123.	Phenytoin	6.12	25	253.0	103.9	181.7
124.	Carisoprodol	6.13	25	261.1	176.0	62.0
125.	Flurazepam	6.14	25	388.2	315.2	183.0
126.	Chlordiazepoxide	6.14	25	300.1	282.0	227.0
127.	Dextromethorphan	6.16	25	272.2	215.1	170.9
128.	PCP	6.18	25	244.2	86.1	159.1
129.	Tenoxicam	6.18	25	338.1	121.0	95.0
130.	Buspirone	6.20	25	386.3	122.1	95.0
131.	Quetiapine	6.28	25	384.2	253.0	221.2
132.	Norpropoxyphene	6.29	25	326.4	252.0	91.1
133.	Propoxyphene	6.30	25	340.3	265.9	58.1
134.	Asenapine	6.35	25	286.2	165.1	229.1
135.	Ziprasidone	6.40	25	413.2	194.1	130.0
136.	Protriptyline	6.42	25	264.1	191.1	165.2
137.	Promazine	6.42	25	285.1	58.0	86.0
138.	Midazolam	6.43	25	326.2	291.1	248.9
139.	Desipramine	6.43	25	267.1	72.1	193.1
140.	Amoxapine	6.44	25	314.2	271.0	193.1
141.	Sufentanil	6.48	25	387.2	238.1	111.1
142.	Imipramine	6.51	25	281.1	86.2	58.1
143.	Paroxetine	6.51	25	330.2	192.2	70.1
144.	Loxapine	6.52	25	328.1	271.1	193.0
145.	Maprotiline	6.52	25	278.1	250.2	191.0
146.	Duloxetine	6.52	25	298.1	154.1	188.2
147.	Metaxalone	6.52	25	222.1	161.1	77.1
148.	Carbamazepine	6.55	10	237.1	194.1	165.0
149.	Cyclobenzaprine	6.56	25	276.2	215.0	189.0
150.	EDDP	6.57	25	278.2	234.3	249.2
151.	Nortriptyline	6.58	25	264.1	91.1	115.2
152.	Mitragynine	6.59	25	399.3	174.2	159.0
153.	Eslicarbazepine	6.60	25	297.2	194.0	237.1
154.	Amitriptyline	6.65	25	278.1	91.1	202.1
155.	α-Hydroxymidazolam	6.70	25	342.2	324.1	202.9
156.	Trimipramine	6.75	25	295.2	100.2	58.2
157.	N-Desmethylflunitrazepam	6.80	25	300.1	254.1	198.1
158.	Lorazepam	6.82	25	321.1	275.0	229.0
159.	Mesoridazine	6.83	25	387.2	126.1	98.2
160.	Tiagabine	6.89	25	376.2	246.8	111.1
161.	Ketorolac	6.90	25	256.1	104.9	77.0
162.	Chlorpromazine	6.91	25	320.1	58.1	86.1
163.	Loxoprofen*	6.93	200	245.0	83.2	80.9
164.	Clomipramine	6.95	25	315.3	86.0	58.0
165.	Oxazepam	6.96	25	287.1	241.2	268.8
166.	Methadone	6.98	25	310.2	264.9	105.1
167.	Sertraline	6.98	25	306.2	158.9	275.1
168.	Dehydro aripiprazole	7.01	25	446.2	285.0	98.1
169.	Clonazepam	7.01	25	316.1	270.0	214.1
170.	Nitrazepam	7.01	25	282.1	235.9	180.1
171.	Lornoxicam	7.02	100	373.1	121.1	95.0
172.	25I-NBOMe	7.05	25	428.1	121.2	91.1
173.	Salsalate*	7.05	100	256.8	136.8	92.9
174.	Desalkylflurazepam	7.09	25	289.0	140.1	104.0
175.	Tolmetin	7.10	25	258.1	119.1	91.0
176.	α-Hydroxytriazolam	7.12	25	359.1	330.9	175.9
177.	Fluphenazine	7.16	25	438.3	171.1	143.2
178.	2-Hydroxyethylflurazepam	7.16	25	333.1	211.1	109.0
179.	Ketoprofen*	7.17	100	253.0	209.0	-
180.	Naproxen*	7.17	200	229.0	168.9	184.9
181.	EMDP	7.19	25	264.2	235.2	220.3
182.	Aripiprazole	7.20	25	448.2	285.0	176.1
183.	Perphenazine	7.22	25	404.2	171.1	143.2
184.	Etoricoxib	7.24	25	359.2	280.0	279.2
185.	Methaqualone	7.24	25	251.1	91.1	132.2
186.	α-Hydroxyalprazolam	7.25	25	325.1	297.0	216.2
187.	Trifluoperazine	7.28	25	408.2	141.2	113.1
188.	Piroxicam	7.34	25	332.1	95.2	78.1
189.	Ibuprofen*	7.34	200	205.0	160.9	-
190.	Prochlorperazine	7.36	25	374.1	141.0	113.1
191.	Etodolac*	7.36	50	286.0	241.9	212.0
192.	Nordiazepam	7.37	25	271.0	139.9	208.0
193.	Phenazepam	7.39	25	349.1	206.2	179.0
194.	Fenoprofen*	7.40	200	240.9	92.8	-
195.	Zaleplon	7.43	25	306.1	264.0	236.0
196.	Clobazam	7.43	25	301.0	259.1	224.0
197.	Flurbiprofen*	7.48	200	243.0	199.0	196.8
198.	Thiothixene	7.50	25	444.2	221.2	235.0
199.	Flunitrazepam	7.55	25	314.2	267.9	239.1
200.	Meloxicam	7.55	25	352.1	115.0	141.0
201.	Triazolam	7.58	25	343.1	307.9	315.0
202.	Estazolam	7.58	25	295.1	266.9	205.1
203.	Celecoxib	7.60	25	382.2	362.0	300.1
204.	Parecoxib	7.60	25	371.2	234.0	165.1
205.	Temazepam	7.61	25	301.1	255.1	282.9
206.	Sulindac	7.70	25	357.2	233.1	248.0
207.	Alprazolam	7.72	25	309.1	280.9	204.9
208.	Flufenamic acid*	7.75	50	279.9	236.1	176.2
209.	Thioridazine	7.76	25	371.2	126.1	98.1
210.	Diclofenac*	7.78	100	293.9	249.8	-
211.	Nabumetone	7.80	25	229.1	171.1	128.1
212.	Oxaprozin	7.87	25	294.1	103.0	234.2
213.	HU-211	8.03	25	387.3	155.9	128.1
214.	JWH‐200	8.04	25	385.3	155.0	127.1
215.	Diazepam	8.04	25	285.1	192.9	153.9
216.	Mefenamic acid	8.04	25	242.1	224.1	-
217.	Tolfenamic acid*	8.17	50	259.9	215.8	-
218.	Meclofenamic acid*	8.18	200	293.9	257.8	177.7
219.	(+/-)-CP 47,497*	8.27	200	317.1	245.1	159.0
220.	Indomethacin*	8.29	50	356.0	311.8	296.9
221.	Perampanel	8.32	25	350.2	219.1	247.1
222.	(+/-)-CP 47,497 C8 homologue*	8.42	200	331.1	259.0	159.1
223.	11-Nor-9-carboxy-delta-9-THC*	8.44	25	343.0	298.9	244.8
224.	Prazepam	8.51	25	325.2	271.0	139.9
225.	XLR-11	8.60	25	330.3	125.2	144.0
226.	Δ9-THC	8.76	25	315.2	193.0	123.2
227.	UR-144	8.78	25	312.3	125.1	214.1
228.	JWH-250	8.96	25	336.3	120.9	91.1
229.	THCA-A*	9.12	25	357.1	312.9	245.0
230.	JWH-073	9.21	25	328.2	155.0	127.1
231.	JWH‐018	9.35	25	342.3	127.1	155.1

*Analyzed using negative polarity.

Column	Raptor Biphenyl (cat.# 9309A12)
Dimensions:	100 mm x 2.1 mm ID
Particle Size:	2.7 µm
Guard Column:	Raptor Biphenyl EXP guard column cartridge 5 mm, 2.1 mm ID, 2.7 µm (cat.# 9309A0252)
Temp.:	30 °C
Standard/Sample
Diluent:	Water
Inj. Vol.:	5 µL
Mobile Phase
A:	Water + 0.1% formic acid + 2 mM ammonium formate
B:	Methanol + 0.1% formic acid + 2 mM ammonium formate
	Time (min) Flow (mL/min) %A %B 0.00 0.6 95 5 9.00 0.6 0 100 10.00 0.6 0 100 10.01 0.6 95 5 12.00 0.6 95 5

Detector	MS/MS
Ion Mode:	ESI+/ESI-
Mode:	Scheduled MRM
Instrument	UHPLC
Notes	1. Positive and negative polarity data were collected simultaneously from a single injection. 2. Ibuprofen, fosphenytoin, and topiramate degrade quickly in solution. 3. Levorphanol and dextrorphan are enantiomers and are not resolved. 4. Escitalopram is a pure enantiomer and citalopram is a racemic mixture of both enantiomers. These compounds are not resolved. 5. DMAA consists of 4 stereoisomers, 2 of which are partially resolved. 6. Doxepin and desmethylydoxepin consist of a mixture of cis/trans isomers. The isomers are fully resolved and the retention time identifies the main isomer component. 7. Lornoxicam, meloxicam, etodolac, oxaprozin, indomethacin, and mefenamic acid can be detected by positive or negative polarity. The polarity chosen in this chromatogram provides optimal response.

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