Research Progress on the Application of MALDI-MSI in Hair Analysis

doi:10.12116/j.issn.1004-5619.2024.340405

Abstract

Abstract:

Mass spectrometry imaging （MSI） is an emerging high-tech “photography” method combining mass spectrometry and image visualization technologies, which can simultaneously monitor the spatial distribution of multiple molecules in biological samples. In recent years, the characteristics of this technology have been used to visually study the distribution of drugs in hair, among which matrix-assisted laser desorption ionization-mass spectrometry imaging（MALDI-MSI） technology has been most widely applied in hair analysis. Based on the principle of MALDI-MSI technology, this paper discusses the key technical elements of MALDI-MSI technology applied to hair analysis and reviews the research achievements of MSI in hair analysis. It concludes that improving the ionization efficiency, resolution, sensitivity and stability of MALDI-MSI technology remains the future exploration direction, and simplifying data analysis and establishing databases will help promote MALDI-MSI as a routine analytical technique for hair analysis.

Key words: forensic medicine, toxicological analysis, matrix-assisted laser desorption ionization-mass spectrometry imaging （MALDI-MSI）, hair, key technology, data processing, visualization, review

CLC Number:

Jiao-jiao JI, Xin WANG, Jia-man LIN, Duo-qi XU, Hui YAN, Min SHEN. Research Progress on the Application of MALDI-MSI in Hair Analysis[J]. Journal of Forensic Medicine, 2024, 40(6): 542-549.

Figures/Tables 2

References 53

1	PRAGST F， BALIKOVA M A. State of the art in hair analysis for detection of drug and alcohol abuse[J]. Clin Chim Acta，2006，370（1/2）：17-49. doi：10.1016/j.cca.2006.02.019 .
2	AGIUS R， KINTZ P. Guidelines for European workplace drug and alcohol testing in hair[J]. Drug Test Anal，2010，2（8）：367-376. doi：10.1002/dta.147 .
3	KINTZ P， VILLAIN M， CIRIMELE V. Hair analysis for drug detection[J]. Ther Drug Monit，2006，28（3）：442-446. doi：10.1097/01.ftd.0000211811. 27558.b5 .
4	JI J J， XU D Q， YAN H， et al. LC-MS-MS determination of 88 psychotropic drugs in 1，865 hair samples from addicts in drug abstinence[J]. J Anal Toxicol，2023，47（1）：52-58. doi：10.1093/jat/bkac024 .
5	MUSIAŁ J， POWIERSKA-CZARNY J， CZARNY J， et al. One-step extraction and determination of 513 psychoactive substances， drugs， and their metabolites from hair by LC-MS/MS[J]. Arch Toxicol，2022，96（11）：2927-2933. doi：10.1007/s00204-022-03343-w .
6	SPENGLER B. Mass spectrometry imaging of biomolecular information[J]. Anal chem，2015，87（1）：64-82. doi：10.1021/ac504543v .
7	NORRIS J L， CAPRIOLI R M. Imaging mass spectrometry： A new tool for pathology in a molecular age[J]. Proteomics Clin Appl，2013，7（11/12）：733-738. doi：10.1002/prca.201300055 .
8	COLOGNA S M. Mass spectrometry imaging of cholesterol[J]. Adv Exp Med Biol，2019，1115：155-166. doi：10.1007/978-3-030-04278-3_7 .
9	王颂凯，邹宇琛，孙士鹏，等. 质谱成像技术前沿进展及其在药物研究中的应用[J].中国药科大学学报，2023，54（6）：653-661. doi：10.11665/j.issn.1000-5048.2023091901 .
	WANG S K， ZOU Y C， SUN S P， et al. Recent advances in mass spectrometry imaging and its application in drug research[J]. Zhongguo Yaoke Da-xue Xuebao，2023，54（6）：653-661.
10	HANRIEDER J， MALMBERG P， EWING A G. Spatial neuroproteomics using imaging mass spectrometry[J]. Biochim Biophys Acta，2015，1854（7）：718-731. doi：10.1016/j.bbapap.2014.12.026 .
11	BAI H， WANG S， LIU J， et al. Localization of ginsenosides in Panax ginseng with different age by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry imaging[J]. J Chromatogr B Analyt Technol Biomed Life Sci，2016，1026：263-271. doi：10.1016/j.jchromb.2015.09.024 .
12	KAMATA T， SHIMA N， MIKI A， et al. High spatial-resolution matrix-assisted laser desorption/ionization-ion trap-time-of-flight tandem mass spectrometry imaging for depicting longitudinal and transverse distribution of drugs incorporated into hair[J]. Anal Chem，2020，92（8）：5821-5829. doi：10.1021/acs.analchem.9b05401 .
13	LIN H， ZENG X， WANG Q， et al. Identification and imaging of indole-3-carboxamide cannabinoids in hair using matrix-assisted laser-desorption/ionization mass spectrometry[J]. Forensic Toxicol，2020，38（1）：216-226. doi：10.1007/s11419-019-00510-0 .
14	蔡乐斯，霍雨萌，田伟，等. 基质辅助激光解吸电离质谱成像在毒品研究中的应用[J].分析化学，2022，50（7）：973-984. doi：10.19756/j.issn.0253-3820.221037 .
	CAI L S， HUO Y M， TIAN W， et al. Application of matrix-assisted laser desorption ionization mass spectrometry imaging technique in illicit drug research[J]. Fenxi Huaxue，2022，50（7）：973-984.
15	WANG H， WANG Y， WANG G， et al. Matrix-assisted laser-desorption/ionization mass spectrometric imaging of olanzapine in a single hair using esculetin as a matrix[J]. J Pharm Biomed Anal，2017，141：123-131. doi：10.1016/j.jpba.2017.04.015 .
16	SHIMA N， SASAKI K， KAMATA T， et al. Single-hair analysis of zolpidem on the supposition of its single administration in drug-facilitated crimes[J]. Forensic Toxicol，2015，33（1）：122-130. doi：10.1007/s11419-014-0260-7 .
17	HE M J， PU W， WANG X， et al. Comparing DESI-MSI and MALDI-MSI mediated spatial metabolomics and their applications in cancer studies[J]. Front Oncol，2022，12：891018. doi：10.3389/fonc. 2022.891018 .
18	SUSNIAK K， KRYSA M， GIEROBA B， et al. Recent developments of MALDI MSI application in plant tissues analysis[J]. Acta Biochim Pol，2020，67（3）：277-281. doi：10.18388/abp.2020_5394 .
19	YOSHIMURA Y， GOTO-INOUE N， MORIYAMA T， et al. Significant advancement of mass spectrometry imaging for food chemistry[J]. Food Chem，2016，210：200-211. doi：10.1016/j.foodchem.2016.04.096 .
20	FERGUSON L S， WULFERT F， WOLSTENHOLME R， et al. Direct detection of peptides and small proteins in fingermarks and determination of sex by MALDI mass spectrometry profiling[J]. Analyst，2012，137（20）：4686-4692. doi：10.1039/c2an36074h .
21	BRADSHAW R， WOLSTENHOLME R， BLACKLEDGE R D， et al. A novel matrix-assisted laser desorption/ionisation mass spectrometry imaging based metho-dology for the identification of sexual assault suspects[J]. Rapid Commun Mass Spectrom，2011，25（3）：415-422. doi：10.1002/rcm.4858 .
22	周莉英，王鑫，向平. 质谱成像技术及其在法医毒理学中的应用[J].法医学杂志，2021，37（3）：402-411. doi：10.12116/j.issn.1004-5619.2020.300502 .
	ZHOU L Y， WANG X， XIANG P. Mass spectrometry imaging and its application in forensic toxicology[J]. Fayixue Zazhi，2021，37（3）：402-411.
23	KARAS M， HILLENKAMP F. Laser desorption ionization of proteins with molecular masses exceeding 10，000 daltons[J]. Anal Chem，1988，60（20）：2299-2301. doi：10.1021/ac00171a028 .
24	VOGLIARDI S， FAVRETTO D， FRISON G， et al. A fast screening MALDI method for the detection of cocaine and its metabolites in hair[J]. J Mass Spectrom，2009，44（1）：18-24. doi：10.1002/jms. 1463 .
25	MIKI A， KATAGI M， KAMATA T， et al. MALDI-TOF and MALDI-FTICR imaging mass spectrometry of methamphetamine incorporated into hair[J]. J Mass Spectrom，2011，46（4）：411-416. doi：10.1002/jms.1908 .
26	MIKI A， KATAGI M， SHIMA N， et al. Imaging of methamphetamine incorporated into hair by MALDI-TOF mass spectrometry[J]. Forensic Toxicol，2011，29（2）：111-116. doi：10.1007/s11419-011-0109-2 .
27	PORTA T， GRIVET C， KRAEMER T， et al. Single hair cocaine consumption monitoring by mass spectrometric imaging[J]. Anal Chem，2011，83（11）：4266-4272. doi：10.1021/ac200610c .
28	KUWAYAMA K， MIYAGUCHI H， IWATA Y T， et al. Time-course measurements of drug concentrations in hair and toenails after single administrations of pharmaceutical products[J]. Drug Test Anal，2017，9（4）：571-577. doi：10.1002/dta.1991 .
29	JI J J， LIN J M， WANG X， et al. Estimation of the time of zolpidem intake and differentiation between consumption and external contamination using MALDI-MSI for investigations on single hair sam-ples[J]. J Pharm Biomed Anal，2024，248：116272. doi：10.1016/j.jpba.2024.116272 .
30	KUWAYAMA K， MIYAGUCHI H， KANAMORI T， et al. Development of an improved method to estimate the days of continuous drug ingestion， based on the micro-segmental hair analysis[J]. Drug Test Anal，2021，13（7）：1295-1304. doi：10.1002/dta. 3025 .
31	KAMATA T， SHIMA N， SASAKI K， et al. Time-course mass spectrometry imaging for depicting drug incorporation into hair[J]. Anal Chem，2015，87（11）：5476-5481. doi：10.1021/acs.analchem.5b00971 .
32	KERNALLÉGUEN A， ENJALBAL C， ALVAREZ J C， et al. Synthetic cannabinoid isomers characterization by MALDI-MS³ imaging： Application to single scalp hair[J]. Anal Chim Acta，2018，1041：87-93. doi：10.1016/j.aca.2018.09.036 .
33	NAKANISHI T， NIRASAWA T， TAKUBO T. Quantitative mass barcode-like image of nicotine in single longitudinally sliced hair sections from long-term smokers by matrix-assisted laser desorption time-of-flight mass spectrometry imaging[J]. J Anal Toxicol，2014，38（6）：349-353. doi：10.1093/jat/bku032 .
34	FLINDERS B， CUYPERS E， ZEIJLEMAKER H， et al. Preparation of longitudinal sections of hair samples for the analysis of cocaine by MALDI-MS/MS and TOF-SIMS imaging[J]. Drug Test Anal，2015，7（10）：859-865. doi：10.1002/dta.1812 .
35	KERNALLÉGUEN A， STEINHOFF R， BACHLER S， et al. High-throughput monitoring of cocaine and its metabolites in hair using microarrays for mass spectrometry and matrix-assisted laser desorption/ionization-tandem mass spectrometry[J]. Anal Chem，2018，90（3）：2302-2309. doi：10.1021/acs.analchem. 7b04693 .
36	BEASLEY E， FRANCESE S， BASSINDALE T. Detection and mapping of cannabinoids in single hair samples through rapid derivatization and matrix-assisted laser desorption ionization mass spectrome-try[J]. Anal Chem，2016，88（20）：10328-10334. doi：10.1021/acs.analchem.6b03551 .
37	VOGLIARDI S， FAVRETTO D， FRISON G， et al. Validation of a fast screening method for the detection of cocaine in hair by MALDI-MS[J]. Anal Bioanal Chem，2010，396（7）：2435-2440. doi：10.1007/s00216-009-3387-3 .
38	POETZSCH M， BAUMGARTNER M R， STEUER A E， et al. Segmental hair analysis for differentiation of tilidine intake from external contamination using LC-ESI-MS/MS and MALDI-MS/MS imaging[J]. Drug Test Anal，2015，7（2）：143-149. doi：10.1002/dta.1674 .
39	POETZSCH M， STEUER A E， ROEMMELT A T， et al. Single hair analysis of small molecules using MALDI-triple quadrupole MS imaging and LC-MS/MS： Investigations on opportunities and pitfalls[J]. Anal Chem，2014，86（23）：11758-11765. doi：10.1021/ac503193w .
40	BUCHBERGER A R， DELANEY K， JOHNSON J， et al. Mass spectrometry imaging： A review of emerging advancements and future insights[J]. Anal Chem，2018，90（1）：240-265. doi：10.1021/acs.anal chem.7b04733 .
41	CRISTONI S， MOLIN L， CROTTI S， et al. Sieve-based device for MALDI sample preparation. Ⅱ. Instrumental parameterization[J]. J Mass Spectrom，2009，44（11）：1579-1586. doi：10.1002/jms.1637 .
42	COHEN S L， CHAIT B T. Influence of matrix solution conditions on the MALDI-MS analysis of peptides and proteins[J]. Anal Chem，1996，68（1）：31-37. doi：10.1021/ac9507956 .
43	KERNALLÉGUEN A， KINTZ P， LEONETTI G， et al. Recent trends in MALDI-MS drugs analysis in human hair： Pre-analytical and analytical challenges and pitfalls[J]. J Anal Toxicol，2023，47（5）：417-428. doi：10.1093/jat/bkad015 .
44	MUSSHOFF F， ARREY T， STRUPAT K. Determination of cocaine， cocaine metabolites and cannabinoids in single hairs by MALDI Fourier transform mass spectrometry — Preliminary results[J]. Drug Test Anal，2013，5（5）：361-365. doi：10.1002/dta.1453 .
45	ERNE R， BERNHARD L， KAWECKI M， et al. Using time-of-flight secondary ion mass spectrome-try （ToF-SIMS） and matrix assisted laser desorption/ionization mass spectrometry （MALDI-MS） for investigations on single hair samples to solve the contamination versus incorporation issue of hair analysis in the case of cocaine and methadone[J]. Analyst，2020，145（14）：4906-4919. doi：10.1039/c9 an02577d .
46	ERNE R， BERNARD L， STEUER A E， et al. Hair analysis： Contamination versus incorporation from the circulatory system — Investigations on single hair samples using time-of-flight secondary ion mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry[J]. Anal Chem，2019，91（6）：4132-4139. doi：10.1021/acs.analchem. 8b05866 .
47	SHEN M， XIANG P， SHI Y， et al. Mass imaging of ketamine in a single scalp hair by MALDI-FTMS[J]. Anal Bioanal Chem，2014，406（19）：4611-4616. doi：10.1007/s00216-014-7898-1 .
48	WANG H， WANG Y. Matrix-assisted laser desorption/ionization mass spectrometric imaging for the rapid segmental analysis of methamphetamine in a single hair using umbelliferone as a matrix[J]. Anal Chim Acta，2017，975：42-51. doi：10.1016/j.aca.2017. 04.012 .
49	FLINDERS B， BEASLEY E， VERLAAN R M， et al. Optimization of sample preparation and instrumental parameters for the rapid analysis of drugs of abuse in hair samples by MALDI-MS/MS imaging[J]. J Am Soc Mass Spectrom，2017，28（11）：2462-2468. doi：10.1007/s13361-017-1766-0 .
50	RUSSO C， BRICKELBANK N， DUCKETT C， et al. Quantitative investigation of terbinafine hydrochloride absorption into a living skin equivalent model by MALDI-MSI[J]. Anal Chem，2018，90（16）：10031-10038. doi：10.1021/acs.analchem.8b02648 .
51	VILLMANN T， SCHLEIF F M， KOSTRZEWA M， et al. Classification of mass-spectrometric data in clinical proteomics using learning vector quantization methods[J]. Brief Bioinform，2008，9（2）：129-143. doi：10.1093/bib/bbn009 .
52	覃露媛，王闯，徐斌，等. MALDI质谱成像中的关键技术探讨及其研究进展[J].药学学报，2023，58（1）：63-75. doi：10.16438/j.0513-4870.2022-0981 .
	QIN L Y， WANG C， XU B， et al. Exploration and advance of key techniques in MALDI mass spectrometry imaging[J]. Yaoxue Xuebao，2023，58（1）：63-75.
53	PATTERSON N H， DOONAN R J， DASKALO-POULOU S S， et al. Three-dimensional imaging MS of lipids in atherosclerotic plaques： Open-source methods for reconstruction and analysis[J]. Proteomics，2016，16（11/12）：1642-1651. doi：10.1002/pmic.201500490 .

序号	基质	喷涂方式	分析物	文献
1	CHCA	自动喷雾器（ImagePrep）	甲氧那明	[31]
2	CHCA	薄层色谱法	可卡因	[27]
3	CHCA	自动喷雾器（SunCollect）	四氢大麻酚、大麻二酚	[36]
4	CHCA	自制尖头点涂	可卡因、苯甲酰爱康宁	[44]
5	CHCA	薄层色谱法	替利定、去甲替利定	[38]
6	CHCA	自动喷雾器（ImagePrep）	可卡因	[34]
7	CHCA	薄层色谱法	可卡因、美沙酮	[45]
8	CHCA	薄层色谱法	唑吡坦	[46]
9	CHCA	自制尖头点涂	氯胺酮	[47]
10	七叶苷	自制尖头点涂	奥氮平	[15]
11	伞形酮	自制尖头点涂	甲基苯丙胺	[48]

序号	基质	喷涂方式	分析物	文献
1	CHCA	自动喷雾器（ImagePrep）	甲氧那明	[31]
2	CHCA	薄层色谱法	可卡因	[27]
3	CHCA	自动喷雾器（SunCollect）	四氢大麻酚、大麻二酚	[36]
4	CHCA	自制尖头点涂	可卡因、苯甲酰爱康宁	[44]
5	CHCA	薄层色谱法	替利定、去甲替利定	[38]
6	CHCA	自动喷雾器（ImagePrep）	可卡因	[34]
7	CHCA	薄层色谱法	可卡因、美沙酮	[45]
8	CHCA	薄层色谱法	唑吡坦	[46]
9	CHCA	自制尖头点涂	氯胺酮	[47]
10	七叶苷	自制尖头点涂	奥氮平	[15]
11	伞形酮	自制尖头点涂	甲基苯丙胺	[48]

序号	MALDI仪器	激光波长/nm	激光斑点大小/μm	激光频率/Hz	分辨率/μm	文献
1	ultrafleXtreme MALDI-TOF/TOF质谱仪	355	直径约90	1 000	100	[31]
2	MALDI FlashQuant Workstation	355	100×200	1 000	100或200	[38-39，45]
3	MALDI SYNAPT HDMS	355	100×150	200	150×50	[34]
4	MALDI SolariX FTICR	355	直径30	1 000	500	[25]
5	MALDI SolariX FTICR	355	直径100	25	500	[48]
6	MALDI-QqQ_LIT	355	200×100	1 000	1 000	[27]
7	iMScope TRIO MALDI-IT-TOF	355	直径5、10、50	1 000	5、10、50	[12]
8	MALDI-QSTAR Pulsar Ⅰ	355	100×150	1 000	100×150	[49]

序号	MALDI仪器	激光波长/nm	激光斑点大小/μm	激光频率/Hz	分辨率/μm	文献
1	ultrafleXtreme MALDI-TOF/TOF质谱仪	355	直径约90	1 000	100	[31]
2	MALDI FlashQuant Workstation	355	100×200	1 000	100或200	[38-39，45]
3	MALDI SYNAPT HDMS	355	100×150	200	150×50	[34]
4	MALDI SolariX FTICR	355	直径30	1 000	500	[25]
5	MALDI SolariX FTICR	355	直径100	25	500	[48]
6	MALDI-QqQ_LIT	355	200×100	1 000	1 000	[27]
7	iMScope TRIO MALDI-IT-TOF	355	直径5、10、50	1 000	5、10、50	[12]
8	MALDI-QSTAR Pulsar Ⅰ	355	100×150	1 000	100×150	[49]

[1]	Zhen-shuo GUO, Wen-jia DUAN, Yu LIU, Yi-ling TANG, Hui YAN. Research Progress on the Analysis of Anabolic Androgenic Steroids in Biological Samples Based on High Resolution Mass Spectrometry [J]. Journal of Forensic Medicine, 2024, 40(6): 533-541.
[2]	Si-yang HE, Qian-ya DENG, Shui-qing ZHENG, Chun-fang NI, Wen-juan SUN, Fang-qi CAO, Chen LIANG, Fei-jun GONG. Identification of a Novel Synthetic Cathinone CMMP [J]. Journal of Forensic Medicine, 2024, 40(6): 550-556.
[3]	Xian-yu FAN, Xue-yan ZHU, Xin WANG, Ping XIANG, Jun-bo ZHAO. High Resolution Mass Spectrometry Fragmentation Rules of Etomidate and Its Structural Analogues [J]. Journal of Forensic Medicine, 2024, 40(6): 557-563.
[4]	Zhu-tao GUO, Qian-ya DENG, Si-yang HE, Shui-qing ZHENG, Rong WANG, Wen-juan SUN, Chen LIANG, Chun-fang NI. Rapid Screening of 60 Types of Natural Toxins in Whole Blood by UPLC-Q/Orbitrap HRMS [J]. Journal of Forensic Medicine, 2024, 40(6): 564-568.
[5]	Ying ZHANG, Wen-fang ZHANG, Duo-qi XU, Shi-yang QIN, Shi-yun YANG, Jing QIAO. Analysis of In Vitro Mirtazapine Metabolites in Human Liver Microsomes by LC-HRMS [J]. Journal of Forensic Medicine, 2024, 40(6): 569-574.
[6]	Guo-qing GAO, Shuo YANG, Li-ying ZHOU, Shi-bei DU, Yan SHI. In Vivo Analysis of New Psychoactive Substances： Nitazenes [J]. Journal of Forensic Medicine, 2024, 40(6): 597-607.
[7]	Hong-xia HAO, Jie-min CHEN, Xiao-ying YU, Meng WANG, Zhi-lu ZHOU, Yan-liang SHENG, Wen-tao XIA. Estimation of Visual Acuity after Recovery from Different Degrees of Ocular Trauma Using Pattern Visual Evoked Potential [J]. Journal of Forensic Medicine, 2024, 40(5): 447-453.
[8]	Zhi YAN, Xun-ming JI, Xiao HE, Xiao-jing ZHANG, Lei WAN, Hong ZHANG, Mei TIAN, Bin CONG. Progress and Application Prospects of Forensic Molecular Imaging Technology in Living Individual Examination [J]. Journal of Forensic Medicine, 2024, 40(5): 476-483.
[9]	Jing LIU, Zheng WANG, Yi-ping HOU, Lin-chuan LIAO. The Impact of STR Mutations on Kinship Identification [J]. Journal of Forensic Medicine, 2024, 40(5): 484-491.
[10]	Qi-rui HAN, Wen-ji ZHANG, Hao-yang LI, Ying-chao LUO. Current Status and Prospects of Bloodstain Age Estimation Technology [J]. Journal of Forensic Medicine, 2024, 40(5): 468-475.
[11]	Tian-fu HE, Huan-hui ZHU, Yuan-yuan TIAN, Yin-shuang JIN, Xian-wen LIN, Song-cai WANG. Detection of Etomidate and Etomidate Acid in Urine Using HPLC-MS/MS Method [J]. Journal of Forensic Medicine, 2024, 40(5): 454-460.
[12]	Hao-jie QIN, Yuan-yuan LIU, En-hao FU, Ya-wen LIU, Zhi-ling TIAN, He-wen DONG, Tai-ang LIU, Dong-hua ZOU, Yi-bin CHENG, Ning-guo LIU. Intelligent Recognition and Segmentation of Blunt Craniocerebral Injury CT Images Based on DeepLabV3+ Model [J]. Journal of Forensic Medicine, 2024, 40(5): 419-429.
[13]	Jing-chen GE, Min SHANG, Ming-yang YAO, Ming-fei WEI, Jun-zhan SHI, Ze-wei YAO, Jia-yin SHI, Fan LI. Application of MSCT Image Post-Processing Techniques in the Identification of Rib Fracture Malunion [J]. Journal of Forensic Medicine, 2024, 40(4): 324-329.
[14]	Yu-jiao WU, Yue-qin ZHOU, Yi-wen SHEN, Jie-qing JIANG. Analysis of 39 Forensic Clinical Sex Identification Cases after Sex Reassignment Surgery [J]. Journal of Forensic Medicine, 2024, 40(4): 365-371.
[15]	Ming-hui JIN, Ya LI, Shao-hua YI. Research Progress on the Application of Human Body Surface Microbiome to Forensic Individual Identification [J]. Journal of Forensic Medicine, 2024, 40(4): 379-386.