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=== Legal === This technique is also used for detection of [[Prohibition of drugs|illicit drugs]] in various samples.<ref>{{Cite journal |last1=Merone |first1=Giuseppe M. |last2=Tartaglia |first2=Angela |last3=Rossi |first3=Sandra |last4=Santavenere |first4=Francesco |last5=Bassotti |first5=Elisa |last6=D'Ovidio |first6=Cristian |last7=Bonelli |first7=Martina |last8=Rosato |first8=Enrica |last9=de Grazia |first9=Ugo |last10=Locatelli |first10=Marcello |last11=Savini |first11=Fabio |date=2021 |title=Fast Quantitative LC-MS/MS Determination of Illicit Substances in Solid and Liquid Unknown Seized Samples |journal=Analytical Chemistry |language=en |volume=93 |issue=49 |pages=16308–16313 |doi=10.1021/acs.analchem.1c03310 |issn=0003-2700 |pmc=8674870 |pmid=34843645}}</ref> The most common method of drug detection has been an [[immunoassay]].<ref>{{Cite journal|title = An evaluation of the diagnostic accuracy of liquid chromatography-tandem mass spectrometry versus immunoassay drug testing in pain patients|url=http://www.painphysicianjournal.com/current/pdf?article=MTM1MQ%3D%3D&journal=55|journal = Pain Physician|date = 2010-06-01|pmid = 20495592|pages = 273–281|volume = 13|issue = 3|first1 = Amadeo|last1 = Pesce|first2 = Murray|last2 = Rosenthal|first3 = Robert|last3 = West|first4 = Cameron|last4 = West|first5 = Bridgit|last5 = Crews|first6 = Charles|last6 = Mikel|first7 = Perla|last7 = Almazan|first8 = Sergey|last8 = Latyshev}}</ref> This method is much more convenient. However, convenience comes at the cost of specificity and coverage of a wide range of drugs, therefore, HPLC has been used as well as an alternative method. As HPLC is a method of determining (and possibly increasing) purity, using HPLC alone in evaluating concentrations of drugs was somewhat insufficient. Therefore, HPLC in this context is often performed in conjunction with [[mass spectrometry]].<ref>{{Cite journal|title = Screening and confirmation of 62 drugs of abuse and metabolites in urine by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry|journal = Journal of Analytical Toxicology|date = 2013-12-01|pmid = 24084874|pages = 642–651|volume = 37|issue = 9|doi = 10.1093/jat/bkt083|first1 = I.-Lin|last1 = Tsai|first2 = Te-I.|last2 = Weng|first3 = Yufeng J.|last3 = Tseng|first4 = Happy Kuy-Lok|last4 = Tan|first5 = Hsiao-Ju|last5 = Sun|first6 = Ching-Hua|last6 = Kuo|doi-access = free}}</ref> Using [[Liquid chromatography–mass spectrometry|liquid chromatography-mass spectrometry]] (LC-MS) instead of [[Gas chromatography–mass spectrometry|gas chromatography-mass spectrometry]] (GC-MS) circumvents the necessity for derivitizing with acetylating or alkylation agents, which can be a burdensome extra step.<ref>{{Cite journal|title = Automated solid-phase extraction and two-step derivatisation for simultaneous analysis of basic illicit drugs in serum by GC/MS|journal = International Journal of Legal Medicine|date = 2000-01-01|pmid = 10929239|pages = 229–235|volume = 113|issue = 4|first1 = W.|last1 = Weinmann|first2 = M.|last2 = Renz|first3 = S.|last3 = Vogt|first4 = S.|last4 = Pollak|doi=10.1007/s004149900098|s2cid = 20451772}}</ref> LC-MS has been used to detect a variety of agents like doping agents, drug metabolites, glucuronide conjugates, amphetamines, opioids, cocaine, BZDs, ketamine, LSD, cannabis, and pesticides.<ref>{{Cite journal|title = A general screening method for doping agents in human urine by solid phase extraction and liquid chromatography/time-of-flight mass spectrometry|journal = Analytica Chimica Acta|date = 2007-02-28|pmid = 17386652|pages = 94–102|volume = 585|issue = 1|doi = 10.1016/j.aca.2006.12.028|first1 = Marjo|last1 = Kolmonen|first2 = Antti|last2 = Leinonen|first3 = Anna|last3 = Pelander|first4 = Ilkka|last4 = Ojanperä| bibcode=2007AcAC..585...94K }}</ref><ref>{{Cite journal|title = Toxicological screening with formula-based metabolite identification by liquid chromatography/time-of-flight mass spectrometry|journal = Analytical Chemistry|date = 2003-11-01|pmid = 14588010|pages = 5710–5718|volume = 75|issue = 21|doi = 10.1021/ac030162o|first1 = Anna|last1 = Pelander|first2 = Ilkka|last2 = Ojanperä|first3 = Suvi|last3 = Laks|first4 = Ilpo|last4 = Rasanen|first5 = Erkki|last5 = Vuori}}</ref> Performing HPLC in conjunction with mass spectrometry reduces the absolute need for standardizing HPLC experimental runs.
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